US20060002860A1 - Abuse-proofed oral dosage form - Google Patents

Abuse-proofed oral dosage form Download PDF

Info

Publication number
US20060002860A1
US20060002860A1 US10/890,763 US89076304A US2006002860A1 US 20060002860 A1 US20060002860 A1 US 20060002860A1 US 89076304 A US89076304 A US 89076304A US 2006002860 A1 US2006002860 A1 US 2006002860A1
Authority
US
United States
Prior art keywords
dosage form
optionally
form according
delayed
release
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10/890,763
Inventor
Johannes Bartholomaus
Heinrich Kugelmann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Gruenenthal GmbH
Original Assignee
Gruenenthal GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Gruenenthal GmbH filed Critical Gruenenthal GmbH
Assigned to GRUNENTHAL GMBH reassignment GRUNENTHAL GMBH ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BARTHOLOMAUS, JOHANNES DR., KUGELMANN, HEINRICH
Priority to PCT/EP2005/006984 priority Critical patent/WO2006002884A1/en
Priority to CN2005800292367A priority patent/CN101027044B/en
Priority to EP05769988.6A priority patent/EP1765303B2/en
Priority to DK05769988.6T priority patent/DK1765303T4/en
Priority to SI200531671T priority patent/SI1765303T2/en
Priority to FIEP05769988.6T priority patent/FI1765303T4/en
Priority to CA002572491A priority patent/CA2572491A1/en
Priority to PT57699886T priority patent/PT1765303E/en
Priority to PL05769988.6T priority patent/PL1765303T5/en
Priority to ES05769988T priority patent/ES2402192T5/en
Priority to JP2007518528A priority patent/JP5259183B2/en
Priority to ARP050102718A priority patent/AR049562A1/en
Priority to MX2007000009A priority patent/MX2007000009A/en
Priority to RU2007103707/15A priority patent/RU2396944C2/en
Priority to AU2005259476A priority patent/AU2005259476B2/en
Priority to PE2005000760A priority patent/PE20060523A1/en
Publication of US20060002860A1 publication Critical patent/US20060002860A1/en
Assigned to GRUNENTHAL GMBH reassignment GRUNENTHAL GMBH ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ARKENAU-MARIC, ELISABETH DR.
Priority to IL180470A priority patent/IL180470A0/en
Priority to HK07110602.2A priority patent/HK1107930A1/en
Priority to US12/140,470 priority patent/US20080248113A1/en
Assigned to JPMORGAN CHASE BANK, N.A., AS ADMINISTRATIVE AGENT reassignment JPMORGAN CHASE BANK, N.A., AS ADMINISTRATIVE AGENT CONFIRMATORY GRANT OF SECURITY INTEREST IN UNITED STATES PATENTS (EXCLUSIVELY LICENSED PATENTS) Assignors: ENDO PHARMACEUTICALS INC.
Assigned to MORGAN STANLEY SENIOR FUNDING, INC., AS ADMINISTRATIVE AGENT reassignment MORGAN STANLEY SENIOR FUNDING, INC., AS ADMINISTRATIVE AGENT SECURITY INTEREST IN EXCLUSIVELY LICENSED PATENTS Assignors: ENDO PHARMACEUTICALS INC.
Assigned to ENDO PHARMACEUTICALS INC. reassignment ENDO PHARMACEUTICALS INC. RELEASE OF SECURITY INTEREST IN EXCLUSIVELY LICENSED PATENTS RECORDED AT REEL/FRAME 25456/172 Assignors: JPMORGAN CHASE BANK N.A., AS ADMINISTRATIVE AGENT
Priority to CY20131100249T priority patent/CY1113847T1/en
Priority to US13/897,746 priority patent/US20130251643A1/en
Priority to US14/143,487 priority patent/US20140112989A1/en
Assigned to ENDO PHARMACEUTICALS SOLUTIONS INC. reassignment ENDO PHARMACEUTICALS SOLUTIONS INC. RELEASE OF PATENT SECURITY INTEREST IN EXCLUSIVELY LICENSED PATENTS Assignors: MORGAN STANLEY SENIOR FUNDING, INC., AS ADMINISTRATIVE AGENT
Assigned to DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT reassignment DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT GRANT OF SECURITY INTEREST IN LICENSED PATENTS Assignors: ENDO PHARMACEUTICALS, INC.
Assigned to ENDO PHARMACEUTICALS INC. reassignment ENDO PHARMACEUTICALS INC. CORRECTIVE ASSIGNMENT TO CORRECT THE NAME OF RECEIVING PARTY IN RELEASE OF PATENT SECURITY INTEREST IN EXCLUSIVELY LICENSED PATENTS PREVIOUSLY RECORDED ON REEL 032380 FRAME 0157. ASSIGNOR(S) HEREBY CONFIRMS THE RELEASE OF SECURITY INTEREST IN EXCLUSIVELY LICENSED PATENTS.. Assignors: MORGAN STANLEY SENIOR FUNDING, INC., AS ADMINISTRATIVE AGENT
Priority to US14/795,900 priority patent/US20150313845A1/en
Priority to US15/057,161 priority patent/US20170209378A9/en
Priority to US15/059,730 priority patent/US20160184295A1/en
Priority to US15/255,534 priority patent/US20160367549A1/en
Assigned to ENDO PHARMACEUTICALS, INC., ENDO PHARMACEUTICALS SOLUTIONS, INC., ASTORA WOMEN'S HEALTH HOLDINGS, LLC reassignment ENDO PHARMACEUTICALS, INC. RELEASE BY SECURED PARTY (SEE DOCUMENT FOR DETAILS). Assignors: DEUTSCHE BANK AG NEW YORK BRANCH
Priority to US15/878,524 priority patent/US20180147149A1/en
Priority to US16/542,808 priority patent/US20200038330A1/en
Priority to US17/010,106 priority patent/US11844865B2/en
Abandoned legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2068—Compounds of unknown constitution, e.g. material from plants or animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2893—Tablet coating processes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids

Definitions

  • dosage forms containing opioids with potential for abuse do not usually give rise to the kick desired by the abuser when taken orally even in abusively high quantities
  • these dosage forms for example in the form of tablets or capsules are also comminuted, e.g. ground, and sniffed by the abuser for the purpose of abuse or the active ingredients are extracted from the powder obtained in this way by means of an aqueous liquid and the resultant solution is administered parenterally, in particular intravenously, optionally after filtration through cotton wool or cellulose wadding.
  • This type of administration produces even more accelerated increase in opioid levels than with oral or nasal abuse, with the result desired by the abuser, namely the “kick” or “rush”.
  • Intravenous administration of such a gel would most probably result in obstruction of blood vessels, associated with serious damage to the health of the abuser.
  • the component (C) may also optionally serve as an additional viscosity-increasing agent, which forms a gel with the assistance of a necessary minimum quantity of aqueous liquid.
  • Component (b) as a viscosity-increasing agent may preferably also serve as a material for a delayed-release matrix, if this is permitted by the structure of the dosage form according to the invention.
  • the dosage form according to the invention may assume multiparticulate form, preferably the form of microtablets, micropellets, granules, spheroids, beads or pellets, optionally packaged in capsules or press-moulded into tablets.
  • the multiparticulate forms preferably have a size or size distribution in the range from 0.1 to 3 mm, particularly preferably in the range from 0.5 to 2 mm.
  • conventional auxiliary substances (B) are optionally also used for the formulation of the dosage form.
  • subunits (X) and (Y) are present in multiparticulate form, wherein microtablets, microcapsules, micropellets, granules, spheroids, beads or pellets are preferred and the same form, i.e. shape, is selected for both subunit (X) and subunit (Y), such that it is not possible to separate subunits (X) from (Y) by mechanical selection.
  • the multiparticulate forms are preferably of a size in the range from 0.1 to 3 mm, preferably of 0.5 to 2 mm.

Abstract

The present invention relates to an abuse-proofed, oral dosage form with controlled opioid-release for once daily administration, characterised in that it comprises at least one opioid with potential for abuse (A), at least one synthetic or natural polymer (C), optionally delayed-release matrix auxiliary substances, physiologically acceptable auxiliary substances (B), optionally a wax (D) and optionally at least one delayed-release coating, component (C) or (D) in each case exhibiting a breaking strength of at least 500 N, preferably of at least 1000 N.

Description

  • The present invention relates to an abuse-proofed oral dosage form with controlled opioid release for once daily administration, comprising at least one opioid with potential for abuse (A), at least one synthetic or natural polymer (C), optionally delayed-release matrix auxiliary substances, optionally physiologically acceptable auxiliary substances (B), optionally a wax (D) and optionally a delayed-release coating, component (C) or (D) in each case exhibiting a breaking strength of at least 500 N, preferably of 1000 N.
  • The name opioids is taken according to the invention to mean compounds which interact with at least one opioid receptor. In particular, with the exception of (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol, the physiologically acceptable salts or derivatives thereof, opioids are taken to mean those compounds which exhibit a potential for abuse.
  • Preferably, opioids are used for combatting pain. To this end, analgesics are frequently used in long-term treatment, for example in the case of chronic pain or pain caused by tumours. In long-term treatment, in particular, it is important to enable the patient to enjoy a good quality of life. The measures which improve the quality of life of a patient include dosage forms which allow once daily administration. However, because of the relatively large quantity of opioid, such dosage forms, which provide delayed release of the active ingredient, are particularly attractive to the abuser who wishes to induce the desired state of narcosis or euphoria as quickly as possible.
  • Since, however, delayed-release dosage forms containing opioids with potential for abuse do not usually give rise to the kick desired by the abuser when taken orally even in abusively high quantities, these dosage forms for example in the form of tablets or capsules are also comminuted, e.g. ground, and sniffed by the abuser for the purpose of abuse or the active ingredients are extracted from the powder obtained in this way by means of an aqueous liquid and the resultant solution is administered parenterally, in particular intravenously, optionally after filtration through cotton wool or cellulose wadding. This type of administration produces even more accelerated increase in opioid levels than with oral or nasal abuse, with the result desired by the abuser, namely the “kick” or “rush”.
  • U.S. Pat. No. 4,070,494 proposed adding a swellable agent to the dosage form in order to prevent abuse. When water is added to extract the opioid, this agent swells and ensures that the filtrate separated from the gel contains only a small quantity of active ingredient.
  • The multilayer tablet disclosed in WO 95/20947 is based on a similar approach to preventing parenteral abuse, said tablet containing the opioid with potential for abuse and at least one gel former, each in different layers.
  • WO 03/015531 A2 discloses another approach to preventing parenteral abuse. A dosage form containing an analgesic opioid and a dye as an aversive agent is described therein. The colour released by tampering with the dosage form is intended to discourage the abuser from using the dosage form which has been tampered with. Another known option for complicating abuse involves adding to the dosage form an antagonist to the opioid, such as for example naloxone or naltexone, or compounds which cause a physiological defence response, such as for example ipecacuanha (ipecac) root, or bitter substances.
  • However, since in most cases of abuse of dosage forms with delayed-release of an opioid, it is still necessary to pulverise the dosage form, it was the object of the present invention to complicate or prevent the pulverisation preceding abuse of the dosage form comprising the means conventionally available for potential abuse and accordingly to provide a dosage form with controlled release of opioids with potential for abuse which ensures the desired therapeutic effect when correctly administered once daily, but from which the opioids cannot be converted into a form suitable for abuse simply by pulverisation.
  • This object was achieved by the preparation of the abuse-proofed oral dosage form, according to the invention, with controlled release of at least one opioid for once daily administration, which dosage form comprises, in addition to at least one opioid and/or at least one of the physiologically acceptable compounds thereof, preferably salts or derivatives, preferably esters or ethers, with potential for abuse (A), at least one synthetic or natural polymer (C), optionally delayed-release matrix auxiliary substances, optionally physiologically acceptable auxiliary substances (B), optionally a wax (D), and optionally at least one delayed-release coating, component (C) or (D) in each case exhibiting a breaking strength of at least 500 N, preferably of 1000 N.
  • By using components (C) and optionally (D) with the stated minimum breaking strength, preferably in such quantities that the dosage form also exhibits such a minimum breaking strength, pulverisation of the dosage form with conventional means and thus subsequent abuse, preferably nasal or parenteral abuse, may be complicated considerably or prevented.
  • Preferably, the components (C) and optionally (D) are present in such quantities that the dosage form exhibits a breaking strength of at least 500 N, preferably of at least 1000 N.
  • Without sufficient comminution of the dosage form, non-hazardous parenteral, in particular intravenous or nasal administration is impossible or extraction of the active ingredient takes the abuser too long, or no or an inadequate kick is obtained on abusive oral administration, since spontaneous release does not occur.
  • According to the invention, comminution is taken to mean pulverisation of the dosage form with conventional means which are available to an abuser, such as for example a pestle and mortar, a hammer, a mallet or other usual means for pulverisation by application of force.
  • The dosage form according to the invention is thus suitable for preventing parenteral, nasal and/or oral abuse of opioids with potential for abuse.
  • Opioids with potential for abuse are known to the person skilled in the art, as are the dosages thereof to be used and processes for the production thereof, and may be present in the dosage form according to the invention as such, in the form of the corresponding derivatives thereof, in particular esters or ethers, or in each case in the form of corresponding physiologically acceptable compounds, in particular in the form of the salts or solvates thereof, as racemates or stereoisomers. The dosage form according to the invention is also suitable for the administration of a plurality of opioids. Preferably it is used to administer to humans or mammals, preferably to humans, a particular opioid for combatting pain for a duration of at least 24 hours.
  • The dosage forms according to the invention are very particularly suitable for preventing the abuse of an opioid which is selected from the group consisting of N-{1-[2-(4Ethyl-5-oxo-2-tetrazolin-1-yl)ethyl]-4-methoxymethyl-4-piperidyl}propionanilide (alfentanil), allylprodine, alphaprodine, anileridine, bemidone, benzylmorphine, bezitramide, 17-cyclopropylmethyl-4,5a-epoxy-7a[(S)-1-hydroxy-1,2,2-trimethyl-propyl]-6-methoxy-6,14-endoethanomorphinan-3-ol (buprenorphine), butorphanol, carfentanil, clofedanol, clonitazene, (−)methyl-[3β-benzoyloxy-2β(1aH,5aH)-tropane carboxylate] (cocaine), 4,5a-epoxy-3-methoxy-17-methyl-7-morphinen-6a-ol (codeine), desomorphine, dextromoramide, (+)-(1-benzyl-3-dimethylamino-2-methyl-1-phenylpropyl)propionate (dextropropoxyphene), dezocine, diampromide, diamorphone, 4,5a-epoxy-3methoxy-17-methyl-6a-morphinanol (dihydrocodeine), 4,5a-epoxy-17-methyl-3,6a-morphinandiol (dihydromorphine), dimenoxadol, dimephetamol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, dihydromorphone, eptazocine, ethoheptazine, ethylmethylthiambutene, 4,5a-epoxy-3-ethoxy-17-methyl-7-morphinen-6a-ol (ethylmorphine), etonitazene, 4,5-epoxy-7-(1-hydroxy-1-methylbutyl)-6-methoxy-17-methyl-6,14-endo-etheno-morphinan-3-ol (etorphine), fenpipramide, N-(1-phenethyl-4-piperidyl)propionanilide (fentanyl), heroin, 4,5-epoxy-3-methoxy-17-methyl-6-morphinanone (hydrocodone), 4,5a-epoxy-3-hydroxy-17-methyl-6-morphinanone (hydromorphone), hydroxypethidine, isomethadone, hydroxymethylmorphinan, 1-[4-(3-hydroxyphenyl)-1-methyl-4-piperidyl]-1-propanone (ketobemidone), (3S,6S)-6-dimethylamino-4,4-diphenylheptan-3-yl acetate (levacetylmethadol), (−)-6-dimethylamino-4,4-diphenol-3-heptanone (levomethadone), (−)-17-methyl-3-morphinanol (levorphanol), levophenacylmorphane, levoxemacin, lofentanil, meperidine, 2-methyl-2-propyltrimethylene dicarbamate, meptazinol, metazocine, methadone, methylmorphine, metapon, 3-methylfentanyl, 4-methylfentanyl, 4,5a-epoxy-17-methyl-7-morphinen-3,6a-diol (morphine), myrophine, nalbuphene, nalorphine, narceine, nicomorphine, 6-dimethylamino-4,4-diphenyl-3-hexanone (normethadone), normorphine, norpipanone, the exudation from plants belonging to the species Papaver somniferum (opium), 4,5a-epoxy-14hydroxy-3-methoxy-17-methyl-6-morphinanone (oxycodone), oxymorphone, plants and parts of plants belonging to the species Papaver somniferum (including the subspecies setigerum) (Papaver somniferum), papaveretum, 1,2,3,4,5,6-hexahydro4,11-dimethyl-3-(3-methyl-2-butenyl)-2,6-methano-3-benzazocin-8-ol (pentazocine), ethyl-(1-methyl-4-phenyl-4-piperidinecarboxylate) (pethidine), phenadoxone, phenomorphane, phenazocine, phenoperidine, piminodine, pholcodeine, 1′-3-cyano-3,3-diphenylpropyl)[1,4′-bipiperidine]-4′-carboxamide (piritramide), proheptazine, promedol, properidine, propoxyphene, methyl {3-[4-methoxycarbonyl-4-(N-phenylpropanamido)piperidino]-propanoate) (remifentanil), N-{4-methoxymethyl-1-[2-(2-thienyl)ethyl]-4-piperidyl}propionanilide (sufentanil), ethyl (2-dimethylamino-1-phenyl-cyclohexene-1-carboxylate) (tilidine, cis and trans), tramadol, (1R,2R,4S)-2-(dimethylamino)methyl-4-(p-fluorobenzyloxy)-1-(m-methoxyphenyl)cyclohexanol, (1R,2R)-3-(2-dimethylaminomethyl-cyclohexyl)phenol, (1S,2S)-3(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol, (2R,3R)-1-dimethylamino-3(3-methoxyphenyl)-2-methyl-pentan-3-ol, (1RS,3RS,6RS)-6-dimethylaminomethyl-1-(3-methoxyphenyl)-cyclohexane-1,3-diol, preferably as racemate, 3-(2-dimethylaminomethyl-1-hydroxy-cyclohexyl)phenyl 2-(4isobutoxy-phenyl)propionate, 3-(2-dimethylaminomethyl-1-hydroxy-cyclohexyl)phenyl 2-(6-methoxy-naphthalen-2-yl)propionate, 3-(2-dimethylaminomethyl-cyclohex-1-enyl)-phenyl 2-(4isobutyl-phenyl)propionate, 3-(2-dimethylaminomethyl-cyclohex-1-enyl)-phenyl 2-(6-methoxy-naphthalen-2-yl)propionate, (RR-SS)-2-acetoxy-4-trifluoromethyl-benzoic acid 3-(2-dimethylaminomethyl-1-hydroxy-cyclohexyl)phenyl ester, (RR-SS)-2-hydroxy-4-trifluoromethyl-benzoic acid 3-(2-dimethylaminomethyl-1-hydroxy-cyclohexyl)phenyl ester, (RR-SS)-4-chloro-2-hydroxy-benzoic acid 3-(2-dimethylaminomethyl-1-hydroxy-cyclohexylphenyl ester, (RR-SS)-2-hydroxy-4-methyl-benzoic acid 3-(2-dimethylaminomethyl-1-hydroxy-cyclohexyl)-phenyl ester, (RR-SS)-2-hydroxy-4-methoxy-benzoic acid 3-(2-dimethylaminomethyl-1-hydroxy-cyclohexyl)-phenyl ester, (RR-SS)-2-hydroxy-5-nitro-benzoic acid 3-(2-dimethylaminomethyl-1-hydroxy-cyclohexyl)-phenyl ester, (RR-SS)-2′,4′-difluoro-3-hydroxy-biphenyl-4-carboxylic acid 3-(2-dimethylaminomethyl-1-hydroxy-cyclohexyl)-phenyl ester together with corresponding stereoisomeric compounds, in each case the corresponding derivatives thereof, in particular amides, esters or ethers, and in each case the physiologically acceptable compounds thereof, in particular the salts and solvates thereof, particularly preferably hydrochlorides.
  • The dosage form according to the invention is particularly suitable for preventing abuse of an opioid active ingredient selected from among the group comprising oxycodone, hydromorphone, morphine, tramadol and the physiologically acceptable derivatives or compounds thereof, preferably the salts and solvates thereof, preferably the hydrochlorides thereof.
  • Furthermore, the dosage form according to the invention is particularly suitable for preventing the abuse of an opioid active ingredient selected from among the group comprising (2R,3R)-1-dimethylamino-3(3-methoxyphenyl)-2-methyl-pentan-3-ol, (1RS,3RS,6RS)-6-dimethylaminomethyl-1-(3-methoxy-phenyl)-cyclohexane-1,3 diol, (1R,2R)-3-(2dimethylaminomethyl-cyclohexyl)phenol, the physiologically acceptable salts thereof, preferably hydrochlorides, physiologically acceptable enantiomers, stereoisomers, diastereomers and racemates and the physiologically acceptable derivatives thereof, preferably ethers, esters or amides.
  • These compounds and the process for the production thereof are described in EP-A-693475 and EP-A-780369 respectively. The corresponding descriptions are hereby introduced as a reference and are deemed to be part of the disclosure.
  • The dosage in the delayed-release dosage form is selected such that once daily administration is ensured. The corresponding dosages are known to the person skilled in the art.
  • In order to achieve the necessary breaking strength of the dosage form according to the invention, at least one synthetic, semi-synthetic or natural polymer (C) is used which has a breaking strength, measured using the method disclosed in the present application, of at least 500 N, preferably of 1000 N. Preferably, at least one polymer is selected for this purpose from among the group comprising polyalkylene oxides, preferably polymethylene oxides, polyethylene oxides, polypropylene oxides, polyolefins, preferably polyethylenes, polypropylenes, polyvinyl chlorides, polycarbonates, polystyrenes, polymethacrylates, the copolymers thereof, and mixtures of at least two of the stated polymer classes or polymers. Particularly preferably, a water-soluble or water-swellable polymer is used. The polymers are distinguished by a molecular weight of at least 0.5 million, preferably of at least 1 million to 15 million, determined by Theological measurement. Particularly preferably suitable are thermoplastic polyalkylene oxides, such as polyethylene oxides, with a molecular weight of at least 0.5 million, preferably of at least 1 million to 15 million, determined by rheological measurement. The polyethylene oxides have a viscosity at 25° C. of 4500 to 17600 cP, measured on a 5 wt. % aqueous solution using a model RVF Brookfield viscosimeter (spindle no. 2/rotational speed 2 rpm), of 400 to 4000 cP, measured on a 2 wt. % aqueous solution using the stated viscosimeter (but with spindle no. 1 or 3/rotational speed 10 rpm) or of 1650 to 10000 cP, measured on a 1 wt. % aqueous solution using the stated viscosimeter (but with spindle no. 2/rotational speed 2 rpm).
  • The polymers are preferably used as powder to produce the dosage form according to the invention.
  • Moreover, in addition to the above-stated polymers, at least one natural, semi-synthetic or synthetic wax (D) with a breaking strength, measured using the method disclosed in the present application, of at least 500 N. preferably of 1000 N, may additionally be used to achieve the necessary breaking strength of the dosage form according to the invention. Waxes with a softening point of at least 60° C. are preferred. Carnauba wax and beeswax are particularly preferred. Carnauba wax is very particularly preferred. Carnauba wax is a natural wax which is obtained from the leaves of the carnauba palm and has a softening point of at most 90° C. When additionally using the wax component, the latter is used together with at least one polymer (C), preferably a polyethylene oxide, in such quantities that the dosage form-exhibits a breaking strength of at least 500 N, preferably of 1000 N, measured using the method stated in the present application.
  • The dosage forms according to the invention are distinguished in that, they cannot be pulverised using conventional comminution tools, such as grinders, due to their hardness. Oral, parenteral, in particular intravenous, or nasal abuse is complicated a very great deal thereby, if not ruled out altogether. However, in order to prevent any possible abuse of the dosage forms according to the invention, in a preferred embodiment, the dosage forms according to the invention may contain further abuse-complicating or -preventing agents as auxiliary substances (B).
  • Thus, the abuse-proofed dosage form according to the invention may comprise, in addition to at least one opioid, at least one polymer (C) and optionally at least one wax (D), at least one of the following components (a)4f) as auxiliary substances (B):
      • (a) at least one substance which irritates the nasal passages and/or pharynx,
      • (b) at least one viscosity-increasing agent, which, with the assistance of a necessary minimum quantity of an aqueous liquid, preferably as an aqueous extract obtained from the dosage form, forms a gel which preferably remains visually distinguishable when introduced into a further quantity of an aqueous liquid,
      • (c) at least one antagonist for the present opioids with potential for abuse,
      • (d) at least one emetic,
      • (e) at least one dye as an aversive agent,
      • (f) at least one bitter substance.
  • The components (a) to (f) are each suitable on their own as additional protection of the dosage form according to the invention against abuse. Accordingly, component (a) is preferably suitable for proofing the dosage form against nasal, oral and/or parenteral, preferably intravenous, abuse, component (b) is preferably suitable for proofing against parenteral, particularly preferably intravenous and/or nasal abuse, component (c) is preferably suitable for proofing against nasal and/or parenteral, particularly preferably intravenous, abuse, component (d) is preferably suitable for proofing against parenteral, particularly preferably intravenous, and/or oral and/or nasal abuse, component (e) is suitable as a visual deterrent against oral or parenteral abuse and component (f) is suitable for proofing against oral or nasal abuse. Through the co-use of at least one of the above-stated components, it is possible to complicate abuse even more effectively for the dosage forms according to the invention.
  • In one embodiment, the dosage form according to the invention may also comprise two or more of components (a)-(f) in a combination, preferably in the combinations (a), (b) and optionally (c) and/or (f) and/or (e) or (a), (b) and optionally (d) and/or (f) and/or (e).
  • In another embodiment, the dosage form according to the invention may comprise all of components (a)-(f).
  • If the dosage form according to the invention comprises component (a) as additional protection against abuse, substances which irritate the nasal passages and/or pharynx which may be considered according to the invention are any substances which, when administered via the nasal passages and/or pharynx, bring about a physical reaction which is either so unpleasant for the abuser that he/she does not wish to or cannot continue administration, for example burning, or physiologically counteracts taking of the corresponding opioid(s) and/or opiate(s), for example due to increased nasal secretion or sneezing. These substances which conventionally irritate the nasal passages and/or pharynx may also bring about a very unpleasant sensation or even unbearable pain when administered parenterally, in particular intravenously, such that the abuser does not wish to or cannot continue taking the substance.
  • Particularly suitable substances which irritate the nasal passages and/or pharynx are those which cause burning, itching, an urge to sneeze, increased formation of secretions or a combination of at least two of these stimuli. Appropriate substances and the quantities thereof which are conventionally to be used are known per se to the person skilled in the art or may be identified by simple preliminary testing.
  • The substance which irritates the nasal passages and/or pharynx of component (a) is preferably based on one or more constituents or one or more plant parts of at least one hot substance drug.
  • Corresponding hot substance drugs are known per se to the person skilled in the art and are described, for example, in “Pharmazeutische Biologie—Drogen und ihre Inhaltsstoffe” by Prof. Dr. Hildebert Wagner, 2nd., revised edition, Gustav Fischer Verlag, Stuttgart-New York, 1982, pages 82 et seq.. The corresponding description is hereby introduced as a reference and is deemed to be part of the disclosure.
  • One or more constituents of at least one hot substance drug selected from the group consisting of Allii sativi bulbus (garlic), Asari rhizoma cum herba (Asarum root and leaves), Calami rhizoma (calamus root), Capsici fructus (capsicum), Capsici fructus acer (cayenne pepper), Curcumae longae rhizoma (turmeric root), Curcumae xanthorrhizae rhizoma (Javanese turmeric root), Galangae rhizoma (galangal root), Myristicae semen (nutmeg), Piperis nigri fructus (pepper), Sinapis albae semen (white mustard seed), Sinapis nigri semen (black mustard seed), Zedoariae rhizoma (zedoary root) and Zingiberis rhizoma (ginger root), particularly preferably from the group consisting of Capsici fructus (capsicum), Capsici fructus acer (cayenne pepper) and Piperis nigri fructus (pepper) may preferably be added as component (a) to the dosage form according to the invention.
  • The constituents of the hot substance drugs preferably comprise o-methoxy(methyl)phenol compounds, acid amide compounds, mustard oils or sulfide compounds or compounds derived therefrom.
  • Particularly preferably, at least one constituent of the hot substance drugs is selected from the group consisting of myristicin, elemicin, isoeugenol, a-asarone, safrole, gingerols, xanthorrhizol, capsaicinoids, preferably capsaicin, capsaicin derivatives, such as N-vanillyl-9E-octadecenamide, dihydrocapsaicin, nordihydrocapsaicin, homocapsaicin, norcapsaicin and nomorcapsaicin, piperine, preferably trans-piperine, glucosinolates, preferably based on non-volatile mustard oils, particularly preferably based on p-hydroxybenzyl mustard oil, methylmercapto mustard oil or methylsulfonyl mustard oil, and compounds derived from these constituents.
  • The dosage form according to the invention may preferably contain the plant parts of the corresponding hot substance drugs in a quantity of 0.01 to 30 wt. %, particularly preferably of 0.1 to 0.5 wt. %, in each case relative to the total weight of the dosage unit. If one or more constituents of corresponding hot substance drugs are used, the quantity thereof in a dosage unit according to the invention preferably amounts to 0.001 to 0.005 wt. %, relative to the total weight of the dosage unit. A dosage unit is taken to mean a separate or separable administration unit, such as for example a tablet or a capsule.
  • Another option for preventing abuse of the dosage form according to the invention consists in adding at least one viscosity-increasing agent as a further abuse-preventing component (b) to the dosage form, which, with the assistance of a necessary minimum quantity of an aqueous liquid, preferably as an aqueous extract obtained from the dosage form, forms a gel which is virtually impossible to administer safely and preferably remains visually distinguishable when introduced into a further quantity of an aqueous liquid
  • For the purposes of the present application, visually distinguishable means that the opioid- or opiate-containing gel formed with the assistance of a necessary minimum quantity of aqueous liquid, when introduced, preferably with the assistance of a hypodermic needle, into a further quantity of aqueous liquid at 37° C., remains substantially insoluble and cohesive and cannot straightforwardly be dispersed in such a manner that it can safely be administered parenterally, in particular intravenously. The material preferably remains visually distinguishable for at least one minute, preferably for at least 10 minutes.
  • Increasing the viscosity to a gel makes it more difficult or even impossible for it to be passed through a needle or injected. If the gel remains visually distinguishable, this means that the gel obtained on introduction into a further quantity of aqueous liquid, for example by injection into blood, initially remains in the form of a largely cohesive thread, which, while it may indeed be broken up mechanically into smaller fragments, cannot be dispersed or even dissolved in such a manner that it can safely be administered parenterally, in particular intravenously. In combination with at least one further present component (a), (d) to (f), this additionally leads to unpleasant burning, vomiting, bad flavour and/or visual deterrence.
  • Intravenous administration of such a gel would most probably result in obstruction of blood vessels, associated with serious damage to the health of the abuser.
  • In order to verify whether a viscosity-increasing agent is suitable as component (b) for use in the dosage form according to the invention, the opioid(s) and/or opiate(s) is(are) mixed with the viscosity-increasing agent and suspended in 10 ml of water at a temperature of 25° C. If this results in the formation of a gel which fulfils the above-stated conditions, the corresponding viscosity-increasing agent is suitable for additionally preventing or averting abuse of the dosage forms according to the invention.
  • If component (b) is added to the dosage form obtained by the process according to the invention, preferably one or more viscosity-increasing agents are used, which are selected from the group comprising microcrystalline cellulose with 11 wt. % carboxymethylcellulose sodium (Avicel® RC 591), carboxymethylcellulose sodium (Blanose®, CMC-Na C300P®, Frimulsion BLC-5®, Tylose C300 P®), polyacrylic acid (Carbopol® 980 NF, Carbopol® 981), locust bean flour (Cesagum® LA-200, Cesagum® LID/150, Cesagum® LN-1), pectins, preferably from citrus fruits or apples (Cesapectin® HM Medium Rapid Set), waxy maize starch (C*Gel 04201®), sodium alginate (Frimulsion ALG (E401)®), guar flour (Frimulsion BM®, Polygum 26/1-75®), iota-carrageenan (Frimulsion D021®), karaya gum, gellan gum (Kelcogel F®, Kelcogel LT100®), galactomannan (Meyprogat 150®), tara stone flour (Polygum 43/1®), propylene glycol alginate (Protanal-Ester SD-LB®), sodium-hyaluronate, tragacanth, tara gum (Vidogum SP 200®), fermented polysaccharide welan gum (K1A96), xanthans such as xanthan gum (Xantural 180®). Xanthans are particularly preferred. The names stated in brackets are the trade names by which the materials are known commercially. In general, a quantity of 0.1 to 5 wt. %, relative to the total quantity of the dosage form, of the stated viscosity-increasing agent(s) is sufficient to fulfil the above-stated conditions.
  • The component (b) viscosity-increasing agents, where provided, are preferably present in the dosage form according to the invention in quantities of =5 mg per dosage unit, i.e. per administration unit.
  • In a particularly preferred embodiment of the present invention, the viscosity-increasing agents used as component (b) are those which, preferably by extraction from the dosage form with the necessary minimum quantity of aqueous liquid, form a gel which encloses air bubbles. The resultant gels are distinguished by a turbid appearance, which provides the potential abuser with an additional optical warning and discourages him/her from administering the gel parenterally.
  • The component (C) may also optionally serve as an additional viscosity-increasing agent, which forms a gel with the assistance of a necessary minimum quantity of aqueous liquid.
  • It is also possible, to arrange the viscosity-increasing component and the other constituents of the dosage form according to the invention spatially separately from one another.
  • Moreover, in order to discourage and prevent abuse, the dosage form according to the invention may furthermore comprise component (c), namely one or more antagonists for the opioid(s) and/or opiate(s) with potential for abuse, wherein the antagonist is preferably spatially separated from the remaining constituents of the dosage form according to the invention and, when correctly used, do not exert any effect.
  • Suitable antagonists for preventing the abuse of opioids are known per se to the person skilled in the art and may be present in the dosage form according to the invention as such or in the form of corresponding derivatives, in particular esters or ethers, or in each case in the form of corresponding physiologically acceptable compounds, in particular in the form of the salts or solvates thereof.
  • The antagonist used is preferably selected from the group comprising naloxone, naltrexone, nalmefene, nalide and nalmexone, in each case optionally in the form of a corresponding physiologically acceptable compound, in particular in the form of a base, a salt or solvate. The corresponding antagonists, where component (c) is provided, are preferably used in a quantity of =1 mg, particularly preferably in a quantity of 3 to 100 mg, very particularly preferably in a quantity of 5 to 50 mg per dosage form, i.e. per administration unit.
  • The dosage form according to the invention preferably comprises the antagonist component in a conventional therapeutic dose known to the person skilled in the art, particularly preferably in a quantity of twice to three times this dose per administration unit.
  • If the combination for additional discouragement and prevention of abuse of the dosage form according to the invention comprises component (d), it may comprise at least one emetic, which is preferably present in a spatially separated arrangement from the other components of the dosage form according to the invention and, when correctly used, is intended not to exert its effect in the body.
  • Suitable emetics for additionally preventing abuse of an opioid are known per se to the person skilled in the art and may be present in the dosage form according to the invention as such or in the form of corresponding derivatives, in particular esters or ethers, or in each case in the form of corresponding physiologically acceptable compounds, in particular in the form of the salts or solvates thereof.
  • An emetic based on one or more constituents of ipecacuanha (ipecac) root, preferably based on the constituent emetine may preferably be considered for the dosage form according to the invention, as are, for example, described in “Pharmazeutische Biologie—Drogen und ihre Inhaltsstoffe” by Prof. Dr. Hildebert Wagner, 2nd, revised edition, Gustav Fischer Verlag, Stuttgart, New York 1982. The corresponding literature description is hereby introduced as a reference and is deemed to be part of the disclosure.
  • The dosage form according to the invention may preferably comprise the emetic emetine as component (d), preferably in a quantity of =3 mg, particularly preferably of =10 mg and very particularly preferably in a quantity of =20 mg per dosage form, i.e. administration unit.
  • Apomorphine may likewise preferably be used as an emetic for additional abuse proofing, preferably in a quantity of preferably =3 mg, particularly preferably of =5 mg and very particularly preferably of =7 mg per administration unit.
  • If the dosage form according to the invention contains component (e) as a further abuse-preventing auxiliary substance, the use of such a dye brings about an intense coloration of a corresponding aqueous solution, in particular when the attempt is made to extract the opioid(s) for parenteral, preferably intravenous administration, which coloration may act as a deterrent to the potential abuser. Oral abuse, which conventionally begins by means of aqueous extraction of the opioid(s), may also be prevented by this coloration. Suitable dyes and the quantities required for the necessary deterrence may be found in WO 03/015531, wherein the corresponding disclosure should be deemed to be part of the present disclosure and is hereby introduced as a reference.
  • If the dosage form according to the invention contains component (f) as a further abuse-preventing auxiliary substance, this addition of at least one bitter substance and the consequent impairment of the flavour of the dosage form additionally prevents oral and/or nasal abuse.
  • Suitable bitter substances and the quantities effective for use may be found in U.S. 2003/0064099, the corresponding disclosure of which should be deemed to be the disclosure of the present application and is hereby introduced as a reference. Suitable bitter substances are preferably aromatic oils, preferably peppermint oil, eucalyptus oil, bitter almond oil, menthol, fruit aroma substances, preferably aroma substances from lemons, oranges, limes, grapefruit or mixtures thereof, and/or denatonium benzoate (Bitrex®). Denatonium benzoate is particularly preferably used.
  • To ensure once daily administration, the dosage form according to the invention comprises the opioid (s) and/or opiate(s) with potential for abuse at least in part in delayed-release form, wherein the delayed release of the active ingredient may be achieved with the assistance of conventional materials and processes known to the person skilled in the art, for example by embedding the opioid(s) in a delayed-release matrix or by applying one or more delayed-release coatings. Opioid release must, however, be controlled such that the abovestated conditions are fulfilled in each case, for example that, in the event of correct administration of the dosage form, the opioid(s) are virtually completely released before the optionally present component (c) and/or (d) can exert an impairing effect. In particular, release of the opioid must ensure analgesic action for at least 24 hours.
  • If release of the opioid(s) from the dosage form according to the invention is controlled with the assistance of at least one delayed-release coating, the delayed-release coating may consist of conventional materials known to the person skilled in the art.
  • In a preferred embodiment of the dosage form according to the invention, the delayed-release coating is preferably based on a water-insoluble, optionally modified natural and/or synthetic polymer or on a natural, semi-synthetic or synthetic wax or on a fat or a fatty alcohol or on a mixture of at least two of the above-stated components.
  • To produce a delayed-release coating, the water-insoluble polymers preferably comprise poly(meth)acrylates, particularly preferably poly(C1-4)-alkyl(meth)acrylates, poly(C1-4)-dialkylamino-(C1-4)-alkyl(meth)acrylates and/or the copolymers thereof, very particularly preferably copolymers of ethyl acrylate and methyl methacrylate with a molar ratio of monomers of 2:1 (Eudragit NE30D®), copolymers of ethyl acrylate, methyl methacrylate and trimethylammonium methyl methacrylate chloride with a molar ratio of monomers of 1:2:0.1 (Eudragit RS®), copolymers of ethyl acrylate, methyl methacrylate and trimethylammonium methyl methacrylate chloride with a molar ratio of monomers of 1:2:0.2 (Eudragit RL®) or a mixture of at least two of these above-stated copolymers. These coating materials are commercially obtainable as 30 wt. % aqueous latex dispersions, i.e. as Eudragit RS30D®, Eudragit NE30D® or Eudragit RL30D® and are preferably also used as such as coating material.
  • Polyvinyl acetates optionally in combination with further auxiliary substances may likewise preferably be used as water-insoluble polymers for the production of a delayed-release coating for the dosage forms according to the invention. These are commercially obtainable as aqueous dispersions containing 27 wt. % of polyvinyl acetate, 2.5 wt. % of povidone and 0.3 wt. % of sodium lauryl sulfate (Kollicoat SR 30 D®).
  • In a further preferred embodiment, the delayed-release coatings for the dosage form according to the invention are based on water-insoluble cellulose derivatives, preferably alkylcelluloses such as for example ethylcellulose, or cellulose esters, such as for example cellulose acetate. The coatings of ethylcellulose or cellulose acetate are preferably applied from an aqueous pseudolatex dispersion. Aqueous ethylcellulose pseudolatex dispersions are commercially obtainable as 30 wt. % dispersions (Aquacoat®) or as 25 wt. % dispersions (Surelease®).
  • If the delayed-release coating is based a water-insoluble, optionally modified natural and/or synthetic polymer, the coating dispersion or solution may comprise, in addition to the corresponding polymer, a conventional physiologically acceptable plasticiser known to the person skilled in the art, in order to reduce the necessary minimum film temperature.
  • Suitable plasticisers are for example lipophilic diesters from an aliphatic or aromatic dicarboxylic acid with C6-C40 and an aliphatic alcohol with C1-C8, such as for example dibutyl phthalate, diethyl phthalate, dibutyl sebacate or diethyl sebacate, hydrophilic or lipophilic esters of citric acid, such as triethyl citrate, tributyl citrate, acetyl tributyl citrate or acetyl triethyl citrate, polyethylene glycols, propylene glycol, esters of glycerol, such as for example triacetin, Myvacet® (acetylated mono- and diglycerides, C23H44O5 to C25H47O7), medium-chain triglycerides (Miglyol®), oleic acid or mixtures of at least two of the stated plasticisers. Aqueous dispersions of Eudragit RS® and optionally Eudragit RL® preferably contain triethyl citrate.
  • Preferably, a delayed-release coating for the dosage form according to the invention contains plasticisers in quantities of 5 to 50 wt. %, particularly preferably of 10 to 40 wt. % and very particularly preferably of 10 to 30 wt. %, relative to the quantity of polymer used. In individual cases, for example for cellulose acetate, it is also possible to use larger quantities of plasticisers.
  • Moreover, a delayed-release coating may comprise further conventional auxiliary substances known to the person skilled in the art, such as for example slip agents, preferably talcum or glycerol monostearate, colouring pigments, preferably iron oxides or titanium dioxide, or surfactants, such as for example Tween 80®.
  • The release profile obtained for the opioid(s) may furthermore be adjusted by conventional options known to the person skilled in the art, such as for example the thickness of the coating or by the use of further auxiliary substances as constituents of the coating. Suitable auxiliary substances are for example hydrophilic or pH-dependent pore formers, such as for example sodium carboxymethylcellulose, cellulose acetate phthalate, hydroxypropylmethylcellulose acetate succinate, lactose, polyethylene glycol or mannitol or water-soluble polymers, such as for example polyvinylpyrrolidone or water-soluble celluloses, preferably hydroxypropylmethylcellulose or hydroxypropylcellulose.
  • The dosage forms according to the invention for release of the oploid(s) may additionally also comprise a coating which is resistant to gastric juices, which dissolves in pH-dependent manner. This coating makes it possible to ensure that the dosage forms according to the invention pass through the stomach undissolved and the opioid(s) is(are) not released until it(they) reach(es) the intestine.
  • The coating resistant to gastric juices is preferably based on methacrylic acid/alkyl methacrylate copolymers, preferably methyl methacrylate, such as methacrylic acid or ethylene methacrylate copolymers with a molar ratio of the particular monomers of 1:1 to 1:2, such as Eudragit L®, Eudragit S®, Eudragit L30D-55®, Eudragit FS®.
  • A delayed-release coating may be applied by conventional methods known to the person skilled in the art, such as for example by spraying of solutions, dispersions or suspensions, by melt methods or by powder application methods. The solutions, dispersions or suspensions may be used in the form of aqueous or organic solutions or dispersions. Aqueous dispersions are preferably used in this connection. Organic solvents which may be used are alcohols, for example ethanol or isopropanol, ketones, such as for example acetone, esters, for example ethyl acetate, wherein alcohols and ketones are preferably used. The coating methods are known from the prior art, for example H. Sucker, Georg Thieme Verlag, 1991, pages 347 et seq.. They are hereby introduced as a reference and are accordingly deemed to be part of the disclosure.
  • If the dosage form according to the invention is in multiparticulate form, the delayed-release coating is preferably applied in such a manner that the multiparticulate forms containing the opioid(s) are coated, after the production thereof, with the particular polymers and optionally further auxiliary substances from aqueous and/or organic media, preferably from aqueous media, with the assistance of the fluidised bed method and the coating is preferably simultaneously dried at conventional temperatures in the fluidised bed.
  • A poly(meth)acrylate-based coating is preferably dried at temperatures in the range from 30 to 50° C., particularly preferably from 35 to 45° C. For cellulose-based coatings, such as for example ethylcellulose, drying preferably proceeds at a temperature in the range from 50 to 80° C., particularly preferably in the range from 55 to 65° C. If necessary, drying may additionally be followed by a temperature-controlled treatment in order to obtain a stable release profile. Delayed release of the active ingredient from the dosage form according to the invention may also be achieved by embedding the opioid(s) in a delayed-release matrix.
  • Materals which may be used for a delayed-release matrix are preferably physiologically acceptable, hydrophilic polymers, preferably cellulose ethers, cellulose esters and/or acrylic resins. Ethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose. hydroxyethylcellulose, methylcellulose, poly(meth)acrylic acid and/or the derivatives thereof, such as the salts, amides or esters thereof, are particularly preferably used.
  • Where hydrophobic compounds are used as the delayed-release matrix, fatty acids, fatty alcohols or corresponding esters or ethers or mixtures thereof may be used. Mono- or diglycerides of C12-C30 fatty acids and/or C12-C30 fatty alcohols and/or waxes or mixtures thereof are particularly preferably used as hydrophobic compounds.
  • It is also possible to use mixtures of the above-stated hydrophilic and hydrophobic matrix materials.
  • Component (b) as a viscosity-increasing agent may preferably also serve as a material for a delayed-release matrix, if this is permitted by the structure of the dosage form according to the invention.
  • Component (C) and the optionally present component (D), which serve to obtain the breaking strength of at least 500 N, preferably of 1000 N, which is necessary according to the invention, may optionally also serve as additional delayed-release matrix materials.
  • Corresponding delayed-release compounds and methods for the delayed release of the dosage forms according to the invention and for the application of coatings which are resistant to gastric juices are known to the person skilled in the art, for example from “Coated Pharmaceutical Dosage Forms—Fundamentals, Manufacturing Techniques, Biopharmaceutical Aspects, Test Methods and Raw Materials” by Kurt H. Bauer, K. Lehmann, Hermann P. Osterwald, Rothgang, Gerhart, 1st edition, 1998, Medpharm Scientific Publishers. The corresponding literature description is hereby introduced as a reference and is deemed to be part of the disclosure.
  • The dosage form according to the invention may assume multiparticulate form, preferably the form of microtablets, micropellets, granules, spheroids, beads or pellets, optionally packaged in capsules or press-moulded into tablets. The multiparticulate forms preferably have a size or size distribution in the range from 0.1 to 3 mm, particularly preferably in the range from 0.5 to 2 mm. Depending on the desired dosage form, conventional auxiliary substances (B) are optionally also used for the formulation of the dosage form.
  • In a particularly preferred embodiment, the dosage form according to the invention assumes the form of a tablet, a capsule or is in the form of an oral osmotic therapeutic system (OROS), preferably if at least one further abuse-preventing component (a)-(f) is also present.
  • The abuse-proofed, solid dosage form according to the invention is preferably produced by mixing components (A), (C) and optionally (D), optionally at least one of the additional abuse-preventing components (a)-(f) and optionally further auxiliary substances (B), in particular the delayed-release matrix compounds, and, with preceding or simultaneous exposure to heat, forming the resultant mixture, optionally after pelletisation, into the dosage form by application of force.
  • Pelletisation may be performed by a melt method or by wet pelletisation.
  • Mixing of components (A), (C) and optionally (D) and of the optionally present further components (a)-(f) and optionally the further auxiliary substances (B), in particular the delayed-release matrix compounds, may proceed in a mixer known to the person skilled in the art. The mixer may, for example, be a roll mixer, shaking mixer, shear mixer or compulsory mixer.
  • The resultant mixture is preferably directly formed into the dosage form according to the invention by application of force with preceding or simultaneous exposure to heat. The mixture may, for example, be formed into tablets by direct tabletting. In direct tabletting with preceding exposure to heat, the material to be press-moulded is heated immediately prior to tabletting at least to the softening temperature of component (C) and then pressed.
  • The resultant mixture of components (A), (C), optionally (D), the optionally present components (a) to (f) and optionally further auxiliary substances (B), in particular the delayed-release matrix compounds, may also first be pelletised and then formed into the dosage form according to the invention by application of force with preceding or simultaneous exposure to heat.
  • It is also possible to form the resultant mixture containing one or more opioid(s) with potential for abuse (A) and optionally physiologically acceptable auxiliary substances (B), such as components (a) to (f) and optionally the delayed-release matrix compounds and at least one synthetic or natural polymer (C) and optionally a wax (D), into the dosage form by application of force, optionally to singulate the formed articles and optionally in each case to grade them by size and, after or during heating to at least the softening point of component (C), to expose them to force until the formed articles exhibit a breaking hardness of at least 500 N, preferably of 1000 N, optionally to provide them with a cover, which optionally has delayed-release properties, and optionally to mix all the formed articles together again.
  • If components (c) and/or (d) and/or (f) are present in the dosage form according to the invention, care must be taken to ensure that they are formulated in such a manner or are present in such a low dose that, when correctly administered, the dosage form is able to bring about virtually no effect which impairs the patient or the efficacy of the opioid(s).
  • If the dosage form according to the invention contains component (d) and/or (f), the dosage must be selected such that, when correctly orally administered, no negative effect is caused. If, however, the intended dosage of the dosage form is exceeded inadvertently, in particular by children, or in the event of abuse, nausea or an inclination to vomit or a bad flavour are produced. The particular quantity of component (d) and/or (f) which can still be tolerated by the patient in the event of correct oral administration may be determined by the person skilled in the art by simple preliminary testing.
  • If, however, irrespective of the fact that the dosage form according to the invention is virtually impossible to pulverise, the dosage form containing the components (c) and/or (d) and/or (f) is provided with protection, these components should preferably be used at a dosage which is sufficiently high that, when abusively administered, they bring about an intense negative effect on the abuser. This is preferably achieved by spatial separation of at least the opioid(s) from components (c) and/or (d) and/or (f), wherein the opioid(s) is/are present in at least one subunit (X) and components (c) and/or (d) and/or (f) is/are present in at least one subunit (Y), and wherein, when the dosage form is correctly administered, components (c), (d) and (f) do not exert their effect on taking and/or in the body and the remaining components of the formulation, in particular component (C), are identical.
  • If the dosage form according to the invention comprises at least 2 of components (c) and (d) or (f), these may each be present in the same or different subunits (Y). Preferably, when present, all the components (c) and (d) and (f) are present in one and the same subunit (Y).
  • In the case of spatial separation into subunit(s) (X) and subunit(s) (Y) and irrespective of the arrangement of these subunits in the dosage form, a subunit (X) contains the active ingredient in delayed-release form, such that said active ingredient ensures controlled release with once daily administration.
  • For the purposes of the present invention, subunits are solid formulations, which in each case, apart from conventional auxiliary substances known to the person skilled in the art, contain the opioid(s), at least one polymer (C) and optionally at least one of the optionally present components (a) and/or (b) and/or (e) or in each case at least one polymer (C) and the antagonist(s) and/or emetic(s) and/or component (e) and/or component (f) and optionally at least one of the optionally present components (a) and/or (b) and optionally the delayed-release matrix compounds. Care must here be taken to ensure that each of the subunits is formulated in accordance with the above-stated process.
  • One substantial advantage of the separated formulation of the opioid(s) from components (c) or (d) or (f) in subunits (X) and (Y) of the dosage form according to the invention is that, when correctly administered, components (c) and/or (d) and/or (f) are hardly released on taking and/or in the body or are released in such small quantities that they exert no effect which impairs the patient or therapeutic success or, on passing through the patient's body, they are only liberated in locations where they cannot be sufficiently absorbed to be effective. When the dosage form is correctly administered, preferably hardly any of components (c) and/or (d) and/or (f) is released into the patient's body or they go unnoticed by the patient.
  • The person skilled in the art will understand that the above-stated conditions may vary as a function of the particular components (c), (d) and/or (f) used and of the formulation of the subunits or the dosage form. The optimum formulation for the particular dosage form may be determined by simple preliminary testing. What is vital is that each subunit contains the polymer (C) and has been formulated in the stated manner.
  • Should, contrary to expectations, the abuser succeed in comminuting such a dosage form according to the invention, which comprises components (c) and/or (e) and/or (d) and/or (f) in subunits (Y), for the purpose of abusing the opioid(s) and obtain a powder which is to be extracted with a suitable extracting agent, not only the opioid(s) but also the particular component (c) and/or (e) and/or (f) and/or (d) will be obtained in a form in which it cannot readily be separated from the opioid(s), such that when the dosage form which has been tampered with is administered, in particular by oral and/or parenteral administration, it will exert its effect immediately on taking and/or in the body combined with an additional negative effect on the abuser corresponding to component (c) and/or (d) and/or (f) or, when the attempt is made to extract the active ingredient, the coloration will act as a deterrent and so prevent abuse of the dosage form.
  • A dosage form according to the invention, in which the opioid(s) is/are spatially separated from components (c), (d) and/or (e), preferably by formulation in different subunits, may be formulated in many different ways, wherein the corresponding subunits may each be present in the dosage form according to the invention in any desired spatial arrangement relative to one another, provided that the above-stated conditions for the release of components (c) and/or (d), on the one hand, and for release of the opioid, namely controlled release for once daily administration, on the other, are fulfilled.
  • The person skilled in the art will understand that component(s) (a) and/or (b) which are optionally also present may preferably be formulated in the dosage form according to the invention both in the particular subunits (X) and (Y) and in the form of independent subunits (Y′) corresponding to subunits (X) and (Y), provided that neither the abuse-proofing nor the opioid release over 24 hours in the event of correct administration is impaired by the nature of the formulation and the polymer (C) is included in the formulation and formulation is carried out in accordance with the above-stated processes.
  • In a preferred embodiment of the dosage form according to the invention, subunits (X) and (Y) are present in multiparticulate form, wherein microtablets, microcapsules, micropellets, granules, spheroids, beads or pellets are preferred and the same form, i.e. shape, is selected for both subunit (X) and subunit (Y), such that it is not possible to separate subunits (X) from (Y) by mechanical selection. The multiparticulate forms are preferably of a size in the range from 0.1 to 3 mm, preferably of 0.5 to 2 mm.
  • The subunits (X) and (Y) in multiparticulate form may also preferably be packaged in a capsule or be press-moulded into a tablet, wherein the final formulation in each case proceeds in such a manner that the subunits (X) and (Y) are also retained in the resultant dosage form.
  • The multiparticulate subunits (X) and (Y) of identical shape should also not be visually distinguishable from one another so that the abuser cannot separate them from one another by simple sorting. This may, for example, be achieved by the application of identical coatings which, apart from this disguising function, may also incorporate further functions, such as, for example, controlled release of one or more opioid(s) or provision of a finish resistant to gastric juices on the particular subunits.
  • In a further preferred embodiment of the present invention, subunits (X) and (Y) are in each case arranged in layers relative to one another.
  • The layered subunits (X) and (Y) are preferably arranged for this purpose vertically or horizontally relative to one another in the dosage form according to the invention, wherein in each case one or more layered subunits (X) and one or more layered subunits (Y) may be present in the dosage form, such that, apart from the preferred layer sequences (X)-(Y) or (X)-(Y)-(X), any desired other layer sequences may be considered, optionally in combination with layers containing components (a) and/or (b).
  • Another preferred dosage form according to the invention is one in which subunit (Y) forms a core which is completely enclosed by the delayed-release subunit (X), wherein a separation layer (Z) may be present between said layers. Such a structure is preferably also suitable for the above-stated multiparticulate forms, wherein both subunits (X) and (Y) and an optionally present separation layer (Z), which must satisfy the hardness requirement according to the invention, are formulated in one and the same multiparticulate form.
  • In a further preferred embodiment of the dosage form according to the invention, the subunit (X) forms a core, which is enclosed by subunit (Y), wherein the latter comprises at least one channel which leads from the core to the surface of the dosage form.
  • The dosage form according to the invention may comprise, between one layer of the subunit (X) and one layer of the subunit (Y), in each case one or more, preferably one, optionally swellable separation layer (Z) which serves to separate subunit (X) spatially from (Y).
  • If the dosage form according to the invention comprises the layered subunits (X) and (Y) and an optionally present separation layer (Z) in an at least partially vertical or horizontal arrangement, the dosage form preferably takes the form of a tablet, a coextrudate or a laminate.
  • In one particularly preferred embodiment, the entirety of the free surface of subunit (Y) and optionally at least part of the free surface of subunit(s) (X) and optionally at least part of the free surface of the optionally present separation layer(s) (Z) may be coated with at least one barrier layer (Z′) which prevents release of component (c) and/or (e) and/or (d) and/or (f). The barrier layer (Z′) must also fulfil the hardness conditions according to the invention.
  • Another particularly preferred embodiment of the dosage form according to the invention comprises a vertical or horizontal arrangement of the layers of subunits (X) and (Y) and at least one push layer (p) arranged therebetween, and optionally a separation layer (Z), in which dosage form the entirety of the free surface of the layer structure consisting of subunits (X) and (Y), the push layer and the optionally present separation layer (Z) is provided with a semipermeable coating (E), which is permeable to a release medium, i.e. conventionally a physiological liquid, but substantially impermeable to the opioid(s) and to component (c) and/or (d) and/or (f), and wherein this coating (E) comprises at least one opening for release of the opioid(s) in the area of subunit (X).
  • A corresponding dosage form is known to the person skilled in the art, for example under the name oral osmotic therapeutic system (OROS), as are suitable materials and methods for the production thereof, inter alia from U.S. Pat. No. 4,612,008, U.S. Pat. No. 4,765,989 and U.S. Pat. No. 4,783,337. The corresponding descriptions are hereby introduced as a reference and are deemed to be part of the disclosure.
  • An osmotic dosage form containing an analgesic opioid and a dye as an aversive agent is likewise known to the person skilled in the art from the prior art (WO 03/015531). The tablet core preferably consists of two layers, an opioid-containing layer and a push layer, wherein the push layer contains the dye as the aversive agent. The corresponding description is hereby introduced as a reference and is deemed to be part of the disclosure.
  • In a further preferred embodiment of the claimed invention, the subunit (X) of the dosage form according to the invention is in the form of a tablet, the edge face and optionally one of the two main faces of which is covered with a barrier layer (Z′) containing component (c) and/or (d) and/or (f).
  • The person skilled in the art will understand that the auxiliary substances of the subunit(s) (X) or (Y) and of the optionally present separation layer(s) (Z) and/or of the barrier layer(s) (Z′) used in formulating the dosage form according to the invention will vary as a function of the arrangement thereof in the dosage form according to the invention, the mode of administration and as a function of the particular opioid, of the optionally present components (a) and/or (b) and/or (e) and of component (c) and/or (d) and/or (f), while maintaining release of the active ingredient over 24 hours. The materials which have the requisite properties are in each case known per se to the person skilled in the art.
  • If release of component (c) and/or (d) and/or (f) from subunit (Y) of the dosage form according to the invention is prevented with the assistance of a cover, preferably a barrier layer, the subunit may consist of conventional materials known to the person skilled in the art, providing that it contains at least one polymer (C) to fulfil the hardness condition of the dosage form according to the invention.
  • If a corresponding barrier layer (Z′) is not provided to prevent release of component (c) and/or (d) and/or (f), the materials of the subunits should be selected such that release of the particular component (c) and/or (d) from subunit (Y) is virtually ruled out.
  • The materials which are stated below to be suitable for production of the barrier layer may preferably be used for this purpose. Preferred materials are those which are selected from the group comprising alkylcelluloses, hydroxyalkylcelluloses, glucans, scleroglucans, mannans, xanthans, copolymers of poly[bis(p-carboxyphenoxy)propane: sebacic acid], preferably in a molar ratio of 20:80 (marketed under the name Polifeprosan 20®), carboxymethylcelluloses, cellulose ethers, cellulose esters, nitrocelluloses, polymers based on (meth)acrylic acid and the esters thereof, polyamides, polycarbonates, polyalkylenes, polyalkylene glycols, polyalkylene oxides, polyalkylene terephthalates, polyvinyl alcohols, polyvinyl ethers, polyvinyl esters, halogenated polyvinyls, polyglycolides, polysiloxanes and polyurethanes and the copolymers thereof.
  • Particularly suitable materials may be selected from the group comprising methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxybutylmethylcellulose, cellulose acetate, cellulose propionate (of low, medium or high molecular weight), cellulose acetate propionate, cellulose acetate butyrate, cellulose acetate phthalate, carboxymethylcellulose, cellulose triacetate, sodium cellulose sulfate, polymethyl methacrylate, polyethyl methacrylate, polybutyl methacrylate, polyisobutyl methacrylate, polyhexyl methacrylate, polyisodecyl methacrylate, polylauryl methacrylate, polyphenyl methacrylate, polymethyl acrylate, polyisopropyl acrylate, polyisobutyl acrylate, polyoctatdecyl acrylate, polyethylene, low density polyethylene, high density polyethylene, polypropylene, polyethylene glycol, polyethylene oxide, polyethylene terephthalate, polyvinyl alcohol, polyvinyl isobutyl ether, polyvinyl acetate and polyvinyl chloride.
  • Particularly suitable copolymers may be selected from the group comprising copolymers of butyl methacrylate and isobutyl methacrylate, copolymers of methyl vinyl ether and maleic acid of high molecular weight, copolymers of methyl vinyl ether and maleic acid monoethyl ester, copolymers of methyl vinyl ether and maleic anhydride and copolymers of vinyl alcohol and vinyl acetate.
  • Further materials which are suitable for formulating the barrier layer are starch-filled polycaprolactone (WO98/20073), aliphatic polyesteramides (DE 19 753 534 A1, DE 19 800 698 A1, EP 0 820 698 A1), aliphatic and aromatic polyester urethanes (DE 19822979), polyhydroxyalkanoates, in particular polyhydroxybutyrates, polyhydroxyvalerates, casein (DE 4 309 528), polylactides and copolylactides (EP 0 980 894 A1). The corresponding descriptions are hereby introduced as a reference and are deemed to be part of the disclosure.
  • The above-stated materials may optionally be blended with further conventional auxiliary substances known to the person skilled in the art, preferably selected from the group consisting of glyceryl monostearate, semi-synthetic triglyceride derivatives, semi-synthetic glycerides, hydrogenated castor oil, glyceryl palmitostearate, glyceryl behenate, polyvinylpyrrolidone, gelatine, magnesium stearate, stearic acid, sodium stearate, talcum, sodium benzoate, boric acid and colloidal silica, fatty acids, substituted triglycerides, glycerides, polyoxyalkylene glycols and the derivatives thereof.
  • If the dosage form according to the invention comprises a separation layer (Z′), said layer, like the uncovered subunit (Y), may preferably consist of the above-stated materials described for the barrier layer. The person skilled in the art will understand that release of the opioid(s) and/or opiate(s) or of component (c) and/or (d) from the particular subunit may be controlled by the thickness of the separation layer.
  • Method for Determining Breaking Strength
  • In order to verify whether a polymer or a wax may be used as component (C) or (D) respectively, the polymer or wax is press-moulded to form a tablet with a diameter of 10 mm and a height of 5 mm using a force of 150 N at a temperature which at least corresponds to the softening point of the polymer or wax and is determined with the assistance of a DSC diagram of the polymer or wax. Using tablets produced in this manner, breaking strength is determined with the apparatus described below in accordance with the method for determining the breaking strength of tablets published in the European Pharmacopoeia 1997, page 143, 144, method no. 2.9.8. The apparatus used for the measurement is a “Zwick Z 2.5” materials tester, Fmax=2.5 kN, draw max. 1150 mm with the setup comprising a column and a spindle, clearance behind of 100 mm, a test speed of 0.1800 mm/min and testControl software. Measurement was performed using a pressure piston with screw-in inserts and a cylinder (diam. 10 mm), a force transducer, (Fmax. 1 kN, diameter=8 mm, class 0.5 from 10 N, class 1 from 2 N to ISO 7500-1, with manufacturer's test certificate M to DIN 55350-18, Zwick gross force Fmax=1.45 kN) (all apparatus from Zwick GmbH & Co. KG, Ulm, Germany).
  • The tablets deemed to be resistant to breaking under a specific load include not only those which have not broken but also those which may have suffered plastic deformation under the action of the force.
  • The breaking strength of the dosage forms according to the invention is determined using the same measurement method.
  • The invention is explained below with reference to Examples. These explanations are given merely by way of example and do not restrict the general concept of the invention.
    • EXAMPLE 1
  • a) Production of an Abuse-proofed Tablet Containing Oxycodone
  • The quantities of oxycodone hydrochloride, polyethylene oxide powder and hydroxypropylmethylcellulose (Metholose 90 SH 100 000) as the delayed-release matrix material listed in Table 1 were mixed in a free-fall mixer. The tabletting tool, which consists of die, top punch and bottom punch with a diameter of 10 mm, was heated to 90° C. in a heating cabinet. 600 mg portions of the powder mixture were press-moulded by means of the heated tool, the pressure being maintained for at least 15 seconds.
    TABLE 1
    Components Per tablet Complete batch
    Oxycodone HCl  80.0 mg  40.0 g
    Polyethylene oxide, NF, MW 7 000 000 470.0 mg 235.0 g
    (Polyox WSR 303, Dow Chemicals)
    Hydroxypropylmethylcellulose 100 000  50.0 mg  25.0 g
    mPas (Metholose 90 SH 100 000)
    Total weight 600.0 mg 300.0 g
  • The breaking strength of the tablets is determined using the above-described method. No breakage occurred when a force of 500 N was applied. The tablets could not be comminuted using a hammer, nor with the assistance of a pestle and mortar.
  • In Vitro Release From the Tablets Produced According to a)
  • In vitro release of oxycodone hydrochloride from the tablets produced according to a) was determined in a paddle stirrer apparatus with sinker according to the method described in the European Pharmacopoeia. The temperature of the release medium was 37° C. and the rotational speed of the stirrer 75 min−1. The release medium used was intestinal juice, pH 6.8. The quantity of oxycodone hydrochloride released in each case into the dissolution medium at any one time was determined by spectrophotometry. The percentage released quantity, relative to the total quantity of oxycodone hydrochloride, at each point in time is shown in Table 2.
    TABLE 2
    Time, minutes Released quantity, wt. %
     30 11
     240 40
     480 61
     720 76
    1080 92
    1440 97

Claims (22)

1. An abuse-proofed oral dosage form with controlled opioid release for once daily administration, characterised in that it comprises at least one opioid with potential for abuse (A) and/or one of the physiologically acceptable compounds thereof, at least one synthetic or natural polymer (C), optionally delayed-release auxiliary substances, optionally physiologically acceptable auxiliary substances (B), optionally a wax (D) and optionally at least one delayed-release coating, component (C) or (D) in each case exhibiting a breaking strength of at least 500 N, preferably of at least 1000 N.
2. A dosage form according to claim 1, characterised in that the opioid is at least one opioid selected from among the group comprising oxycodone, hydromorphone, morphine, tramadol, the stereoisomers thereof, the enantiomers thereof, the diastereomers thereof in any desired mixtures, the physiologically acceptable compounds thereof, preferably salts and solvates and the derivatives thereof, preferably esters or ethers.
3. A dosage form according to claim 1, characterised in that, the opioid used was at least one opioid selected from among the group comprising (2R,3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methyl-pentan-3-ol, (1RS,3RS,6RS)-6-dimethylaminomethyl-1-(3-methoxyphenyl)-cyclohexane-1,3-diol, (1RS,2RS)-3-(2-dimethylaminomenthyl-cyclohexyl)phenol, the physiologically acceptable salts thereof, preferably hydrochlorides, physiologically acceptable enantiomers, stereoisomers, diastereoisomers and racemates and the physiologically acceptable derivatives thereof, preferably ethers, esters or amides.
4. A dosage form according to claim 1, characterised in that it is in the form of a tablet.
5. A dosage form according to claim 1, characterised in that it is in multiparticulate form, preferably in the form of microtablets, micropellets, granules, spheroids, beads or pellets, optionally press-moulded into tablets or packaged in capsules.
6. A dosage form according to claim 1, characterised in that the polymer (C) is at least one polymer selected from among the group comprising polyethylene oxides, polyethylenes, polypropylenes, polyvinyl chlorides, polycarbonates, polystyrenes, polyacrylates, and the copolymers thereof, preferably a polyethylene oxide.
7. A dosage form according to claim 6, characterised in that the polyethylene oxide is of high molecular weight.
8. A dosage form according to claim 6, characterised in that the polymer (C) is a water-soluble or water-swellable polymer.
9. A dosage form according to claim 1, characterised in that the wax (D) is at least one natural, semi-synthetic or synthetic was with a softening point of =60° C.
10. A dosage form according to claim 9, characterised in that the wax (D) is carnauba wax or beeswax.
11. A dosage form according to claim 1, characterised in that the component(s) (C) and optionally (D) are present in such quantities that the dosage form exhibits a breaking strength of at least 500 N, preferably of 1000 N.
12. A dosage form according to claim 1, characterised in that the active ingredient is present in a delayed-release matrix.
13. A dosage form according to claim 1, characterised in that component (C) and/or component (D) also serves as an additional delayed-release component.
14. A dosage form according to claim 1, characterised in that it comprises a delayed-release coating.
15. A dosage form according to claim 1, characterised in that it comprises at least one of the following components (a)-(f) as the auxiliary substance (B):
(a) at least one substance which irritates the nasal passages and/or pharynx,
(b) at least one viscosity-increasing agent, which, with the assistance of a necessary minimum quantity of an aqueous liquid, preferably as an aqueous extract obtained from the dosage form, forms a gel which preferably remains visually distinguishable when introduced into a further quantity of an aqueous liquid,
(c) at least one antagonist for each of the opioids with potential for abuse,
(d) at least one emetic,
(e) at least one dye as an aversive agent,
(f) at least one bitter substance.
16. A dosage form according to claim 1, characterised in that it comprises as the viscosity-increasing agent at least one polymer selected from among the group comprising carboxymethylcellulose sodium, polyacrylic acid, locust bean flour, pectin, waxy maize starch, alginate, guar flour, iota-carrageenan, karaya gum, gellan gum, galactomannan, tara stone flour, propylene glycol alginate, hyaluronate, tragacanth, tara gum, fermented polysaccharide welan gum and xanthan.
17. A dosage form according to claim 1, characterised in that component (C) serves as an additional viscosity-increasing agent.
18. A process for the production of a dosage form according to claim 1, characterised in that
(1) components (A), (C), optionally (B) and optionally (D) and optionally delayed-release matrix compounds are mixed and
(2) the resultant mixture, optionally after pelletisation, is formed into the dosage form by application of force optionally with preceding or simultaneous exposure to heat and is optionally provided with a delayed-release coating.
19. A process according to claim 18, characterised in that pelletisation is performed by a melt method.
20. A process according to claim 18, characterised in that pelletisation is performed by wet method.
21. A process for the production of a dosage form according to claim 1, characterised in that
(1) a mixture containing components (A), (C), optionally (B) and optionally (D) and optionally delayed-release matrix compounds is formed into formed articles by application of force,
(2) the formed articles obtained are optionally singulated and optionally in each case graded by size and
(3) after or during heating to at least the softening point of component (C), the formed articles are exposed to force until the formed articles exhibit breaking hardness of at least 500 N, preferably of 1000 N,
(4) are optionally provided with an optionally delayed-release coating and the formed articles are optionally all mixed together again.
22. A dosage form obtainable by processes according to claim 18.
US10/890,763 2004-07-01 2004-07-14 Abuse-proofed oral dosage form Abandoned US20060002860A1 (en)

Priority Applications (29)

Application Number Priority Date Filing Date Title
AU2005259476A AU2005259476B2 (en) 2004-07-01 2005-06-29 Oral dosage form safeguarded against abuse
CA002572491A CA2572491A1 (en) 2004-07-01 2005-06-29 Oral dosage form safeguarded against abuse
PT57699886T PT1765303E (en) 2004-07-01 2005-06-29 Oral dosage form safeguarded against abuse
EP05769988.6A EP1765303B2 (en) 2004-07-01 2005-06-29 Oral tablet safeguarded against abuse
DK05769988.6T DK1765303T4 (en) 2004-07-01 2005-06-29 ABUSE PROOF, ORAL DISPENSATION FORM
SI200531671T SI1765303T2 (en) 2004-07-01 2005-06-29 Oral dosage form safeguarded against abuse
FIEP05769988.6T FI1765303T4 (en) 2004-07-01 2005-06-29 Oral tablet safeguarded against abuse
PCT/EP2005/006984 WO2006002884A1 (en) 2004-07-01 2005-06-29 Oral dosage form safeguarded against abuse
CN2005800292367A CN101027044B (en) 2004-07-01 2005-06-29 Oral dosage form safeguarded against abuse
PL05769988.6T PL1765303T5 (en) 2004-07-01 2005-06-29 Oral dosage form safeguarded against abuse
ES05769988T ES2402192T5 (en) 2004-07-01 2005-06-29 Oral tablet protected from abuse
JP2007518528A JP5259183B2 (en) 2004-07-01 2005-06-29 Oral dosage form protected against abuse
ARP050102718A AR049562A1 (en) 2004-07-01 2005-06-29 ORAL PHARMACEUTICAL FORMS, WITH CONTROLLED OPIOID RELEASE, PROTECTED AGAINST ABUSE AND PROCEDURE FOR PREPARATION
MX2007000009A MX2007000009A (en) 2004-07-01 2005-06-29 Oral dosage form safeguarded against abuse.
RU2007103707/15A RU2396944C2 (en) 2004-07-01 2005-06-29 Protected against unadministered application peroral medication form
PE2005000760A PE20060523A1 (en) 2004-07-01 2005-06-30 ORAL PHARMACEUTICAL FORMS OF OPIOIDS WITH CONTROLLED RELEASE
IL180470A IL180470A0 (en) 2004-07-01 2006-12-31 Oral dosage form safeguarded against abuse
HK07110602.2A HK1107930A1 (en) 2004-07-01 2007-09-28 Oral dosage form safeguarded against abuse
US12/140,470 US20080248113A1 (en) 2004-07-01 2008-06-17 Abuse-proofed oral dosage form
CY20131100249T CY1113847T1 (en) 2004-07-01 2013-03-26 SAFETY AGAINST ABUSE ORAL ORGANIZATION FOR ADMINISTRATION
US13/897,746 US20130251643A1 (en) 2004-07-01 2013-05-20 Abuse-proofed oral dosage form
US14/143,487 US20140112989A1 (en) 2004-07-01 2013-12-30 Abuse-proofed oral dosage form
US14/795,900 US20150313845A1 (en) 2004-07-01 2015-07-10 Abuse-proofed oral dosage form
US15/057,161 US20170209378A9 (en) 2004-07-01 2016-03-01 Abuse-proofed oral dosage form
US15/059,730 US20160184295A1 (en) 2004-07-01 2016-03-03 Abuse-proofed oral dosage form
US15/255,534 US20160367549A1 (en) 2004-07-01 2016-09-02 Abuse-proofed oral dosage form
US15/878,524 US20180147149A1 (en) 2004-07-01 2018-01-24 Abuse-proofed oral dosage form
US16/542,808 US20200038330A1 (en) 2004-07-01 2019-08-16 Abuse-proofed oral dosage form
US17/010,106 US11844865B2 (en) 2004-07-01 2020-09-02 Abuse-proofed oral dosage form

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102004032049A DE102004032049A1 (en) 2004-07-01 2004-07-01 Anti-abuse, oral dosage form
DE102004032049.7 2004-07-01

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US12/140,470 Division US20080248113A1 (en) 2004-07-01 2008-06-17 Abuse-proofed oral dosage form
US13/897,746 Continuation US20130251643A1 (en) 2004-07-01 2013-05-20 Abuse-proofed oral dosage form

Publications (1)

Publication Number Publication Date
US20060002860A1 true US20060002860A1 (en) 2006-01-05

Family

ID=35508085

Family Applications (11)

Application Number Title Priority Date Filing Date
US10/890,763 Abandoned US20060002860A1 (en) 2004-07-01 2004-07-14 Abuse-proofed oral dosage form
US12/140,470 Abandoned US20080248113A1 (en) 2004-07-01 2008-06-17 Abuse-proofed oral dosage form
US13/897,746 Abandoned US20130251643A1 (en) 2004-07-01 2013-05-20 Abuse-proofed oral dosage form
US14/143,487 Abandoned US20140112989A1 (en) 2004-07-01 2013-12-30 Abuse-proofed oral dosage form
US14/795,900 Abandoned US20150313845A1 (en) 2004-07-01 2015-07-10 Abuse-proofed oral dosage form
US15/057,161 Abandoned US20170209378A9 (en) 2004-07-01 2016-03-01 Abuse-proofed oral dosage form
US15/059,730 Abandoned US20160184295A1 (en) 2004-07-01 2016-03-03 Abuse-proofed oral dosage form
US15/255,534 Abandoned US20160367549A1 (en) 2004-07-01 2016-09-02 Abuse-proofed oral dosage form
US15/878,524 Abandoned US20180147149A1 (en) 2004-07-01 2018-01-24 Abuse-proofed oral dosage form
US16/542,808 Abandoned US20200038330A1 (en) 2004-07-01 2019-08-16 Abuse-proofed oral dosage form
US17/010,106 Active 2025-02-13 US11844865B2 (en) 2004-07-01 2020-09-02 Abuse-proofed oral dosage form

Family Applications After (10)

Application Number Title Priority Date Filing Date
US12/140,470 Abandoned US20080248113A1 (en) 2004-07-01 2008-06-17 Abuse-proofed oral dosage form
US13/897,746 Abandoned US20130251643A1 (en) 2004-07-01 2013-05-20 Abuse-proofed oral dosage form
US14/143,487 Abandoned US20140112989A1 (en) 2004-07-01 2013-12-30 Abuse-proofed oral dosage form
US14/795,900 Abandoned US20150313845A1 (en) 2004-07-01 2015-07-10 Abuse-proofed oral dosage form
US15/057,161 Abandoned US20170209378A9 (en) 2004-07-01 2016-03-01 Abuse-proofed oral dosage form
US15/059,730 Abandoned US20160184295A1 (en) 2004-07-01 2016-03-03 Abuse-proofed oral dosage form
US15/255,534 Abandoned US20160367549A1 (en) 2004-07-01 2016-09-02 Abuse-proofed oral dosage form
US15/878,524 Abandoned US20180147149A1 (en) 2004-07-01 2018-01-24 Abuse-proofed oral dosage form
US16/542,808 Abandoned US20200038330A1 (en) 2004-07-01 2019-08-16 Abuse-proofed oral dosage form
US17/010,106 Active 2025-02-13 US11844865B2 (en) 2004-07-01 2020-09-02 Abuse-proofed oral dosage form

Country Status (13)

Country Link
US (11) US20060002860A1 (en)
CN (1) CN101027044B (en)
CY (1) CY1113847T1 (en)
DE (1) DE102004032049A1 (en)
DK (1) DK1765303T4 (en)
ES (1) ES2402192T5 (en)
HK (1) HK1107930A1 (en)
IL (1) IL180470A0 (en)
MX (1) MX2007000009A (en)
PE (1) PE20060523A1 (en)
PT (1) PT1765303E (en)
RU (1) RU2396944C2 (en)
SI (1) SI1765303T2 (en)

Cited By (81)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050031546A1 (en) * 2003-08-06 2005-02-10 Johannes Bartholomaus Abuse-proffed dosage form
US20050236741A1 (en) * 2004-04-22 2005-10-27 Elisabeth Arkenau Process for the production of an abuse-proofed solid dosage form
US20060002859A1 (en) * 2004-07-01 2006-01-05 Elisabeth Arkenau Process for production of an abuse-proofed solid dosage form
US20060039864A1 (en) * 2004-07-01 2006-02-23 Johannes Bartholomaus Abuse-proofed oral dosage form
US20060188447A1 (en) * 2005-02-04 2006-08-24 Elisabeth Arkenau-Maric Process for the production of an abuse-proofed dosage form
US20060193914A1 (en) * 2005-02-04 2006-08-31 Judy Ashworth Crush resistant delayed-release dosage forms
US20070003616A1 (en) * 2003-12-24 2007-01-04 Elisabeth Arkenau-Maric Process for the production of an abuse-proofed dosage form
US20070020335A1 (en) * 2005-07-07 2007-01-25 Farnam Companies, Inc. Sustained release pharmaceutical compositions for highly water soluble drugs
US20070183980A1 (en) * 2003-08-06 2007-08-09 Elisabeth Arkenau-Maric Dosage form that is safeguarded from abuse
US20080020032A1 (en) * 2006-07-21 2008-01-24 Michael Crowley Hydrophobic abuse deterrent delivery system for hydromorphone
US20080248113A1 (en) * 2004-07-01 2008-10-09 Grunenthal Gmbh Abuse-proofed oral dosage form
US20080280975A1 (en) * 2005-11-02 2008-11-13 Theraquest Biosciences, Inc. Methods of preventing the serotonin syndrome and compositions for use thereof
US20080292665A1 (en) * 2007-05-25 2008-11-27 Kulli John C Simple mechanical procedure and product for deterring substance abuse
US20080311049A1 (en) * 2003-08-06 2008-12-18 Grunenthal Gmbh Abuse-proof dosage form
US20090004267A1 (en) * 2007-03-07 2009-01-01 Gruenenthal Gmbh Dosage Form with Impeded Abuse
US20090022798A1 (en) * 2007-07-20 2009-01-22 Abbott Gmbh & Co. Kg Formulations of nonopioid and confined opioid analgesics
US20090081290A1 (en) * 2006-08-25 2009-03-26 Purdue Pharma L.P. Tamper resistant dosage forms
US20090082466A1 (en) * 2006-01-27 2009-03-26 Najib Babul Abuse Resistant and Extended Release Formulations and Method of Use Thereof
US20090175937A1 (en) * 2007-12-17 2009-07-09 Labopharm, Inc. Misuse Preventative, Controlled Release Formulation
WO2009092601A1 (en) * 2008-01-25 2009-07-30 Grünenthal GmbH Pharmaceutical dosage form
US20090317355A1 (en) * 2006-01-21 2009-12-24 Abbott Gmbh & Co. Kg, Abuse resistant melt extruded formulation having reduced alcohol interaction
EP2143336A1 (en) * 2008-07-08 2010-01-13 Alsiano A/S Powdered chewing gum compositions, the use thereof and a method for preparing such compositions
US20100015222A1 (en) * 2008-03-11 2010-01-21 Depomed, Inc. Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic
US20100172989A1 (en) * 2006-01-21 2010-07-08 Abbott Laboratories Abuse resistant melt extruded formulation having reduced alcohol interaction
US20100181705A1 (en) * 2007-08-17 2010-07-22 Grunenthal Gmbh Star distributor
US20100196474A1 (en) * 2008-03-11 2010-08-05 Depomed, Inc. Gastric Retentive Extended-Release Dosage Forms Comprising Combinations of a Non-Opioid Analgesic and an Opioid Analgesic
US20100210732A1 (en) * 2005-11-02 2010-08-19 Najib Babul Methods of Preventing the Serotonin Syndrome and Compositions for Use Therefor
US20100239662A1 (en) * 2008-12-16 2010-09-23 Miloud Rahmouni Misuse preventative, controlled release formulation
US20100249045A1 (en) * 2005-11-02 2010-09-30 Theraquest Biosciences, Inc. Multimodal Abuse Resistant and Extended Release Opioid Formulations
WO2010151741A1 (en) * 2009-06-25 2010-12-29 Elite Laboratories, Inc. Abuse resistant oral dosage forms
US20110020451A1 (en) * 2009-07-22 2011-01-27 Grunenthal Gmbh Tamper-resistant dosage form for oxidation-sensitive opioids
US20110052685A1 (en) * 2009-08-31 2011-03-03 Depomed, Inc. Gastric retentive pharmaceutical compositions for immediate and extended release of acetaminophen
US20110082214A1 (en) * 2008-05-09 2011-04-07 Gruenthal Gmbh Process for the preparation of a solid dosage form, in particular a tablet, for pharmaceutical use and process for the preparation of a precursor for a solid dosage form, in particular a tablet
US20110187017A1 (en) * 2010-02-03 2011-08-04 Grunenthal Gmbh Preparation of a powdery pharmaceutical composition by means of an extruder
US20110237615A1 (en) * 2008-12-12 2011-09-29 Paladin Labs Inc. Narcotic Drug Formulations with Decreased Abuse Potential
US8075872B2 (en) 2003-08-06 2011-12-13 Gruenenthal Gmbh Abuse-proofed dosage form
US8337888B2 (en) 2001-08-06 2012-12-25 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
WO2013167735A1 (en) 2012-05-11 2013-11-14 Grünenthal GmbH Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc
US8597681B2 (en) 2009-12-22 2013-12-03 Mallinckrodt Llc Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans
US8658631B1 (en) 2011-05-17 2014-02-25 Mallinckrodt Llc Combination composition comprising oxycodone and acetaminophen for rapid onset and extended duration of analgesia
US8741885B1 (en) 2011-05-17 2014-06-03 Mallinckrodt Llc Gastric retentive extended release pharmaceutical compositions
US8808745B2 (en) 2001-09-21 2014-08-19 Egalet Ltd. Morphine polymer release system
US8808740B2 (en) 2010-12-22 2014-08-19 Purdue Pharma L.P. Encased tamper resistant controlled release dosage forms
US8858963B1 (en) 2011-05-17 2014-10-14 Mallinckrodt Llc Tamper resistant composition comprising hydrocodone and acetaminophen for rapid onset and extended duration of analgesia
US8877241B2 (en) 2003-03-26 2014-11-04 Egalet Ltd. Morphine controlled release system
US9005660B2 (en) 2009-02-06 2015-04-14 Egalet Ltd. Immediate release composition resistant to abuse by intake of alcohol
US9023394B2 (en) 2009-06-24 2015-05-05 Egalet Ltd. Formulations and methods for the controlled release of active drug substances
US9044402B2 (en) 2012-07-06 2015-06-02 Egalet Ltd. Abuse-deterrent pharmaceutical compositions for controlled release
US9149533B2 (en) 2013-02-05 2015-10-06 Purdue Pharma L.P. Tamper resistant pharmaceutical formulations
US9198861B2 (en) 2009-12-22 2015-12-01 Mallinckrodt Llc Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans
US9226907B2 (en) 2008-02-01 2016-01-05 Abbvie Inc. Extended release hydrocodone acetaminophen and related methods and uses thereof
US9233073B2 (en) 2010-12-23 2016-01-12 Purdue Pharma L.P. Tamper resistant solid oral dosage forms
US9301918B2 (en) 2013-03-15 2016-04-05 Mallinckrodt Llc Abuse deterrent solid dosage form for immediate release with functional score
US9616030B2 (en) 2013-03-15 2017-04-11 Purdue Pharma L.P. Tamper resistant pharmaceutical formulations
US9636303B2 (en) 2010-09-02 2017-05-02 Gruenenthal Gmbh Tamper resistant dosage form comprising an anionic polymer
US9642809B2 (en) 2007-06-04 2017-05-09 Egalet Ltd. Controlled release pharmaceutical compositions for prolonged effect
US9655853B2 (en) 2012-02-28 2017-05-23 Grünenthal GmbH Tamper-resistant dosage form comprising pharmacologically active compound and anionic polymer
US9675610B2 (en) 2002-06-17 2017-06-13 Grünenthal GmbH Abuse-proofed dosage form
US9694080B2 (en) 2001-09-21 2017-07-04 Egalet Ltd. Polymer release system
US9730885B2 (en) 2012-07-12 2017-08-15 Mallinckrodt Llc Extended release, abuse deterrent pharmaceutical compositions
US9737490B2 (en) 2013-05-29 2017-08-22 Grünenthal GmbH Tamper resistant dosage form with bimodal release profile
US9855263B2 (en) 2015-04-24 2018-01-02 Grünenthal GmbH Tamper-resistant dosage form with immediate release and resistance against solvent extraction
US9872835B2 (en) 2014-05-26 2018-01-23 Grünenthal GmbH Multiparticles safeguarded against ethanolic dose-dumping
US9913814B2 (en) 2014-05-12 2018-03-13 Grünenthal GmbH Tamper resistant immediate release capsule formulation comprising tapentadol
US9993422B2 (en) 2012-04-18 2018-06-12 SpecGx LLC Immediate release, abuse deterrent pharmaceutical compositions
US10064945B2 (en) * 2012-05-11 2018-09-04 Gruenenthal Gmbh Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc
US10080721B2 (en) 2009-07-22 2018-09-25 Gruenenthal Gmbh Hot-melt extruded pharmaceutical dosage form
US10154966B2 (en) 2013-05-29 2018-12-18 Grünenthal GmbH Tamper-resistant dosage form containing one or more particles
US10201502B2 (en) 2011-07-29 2019-02-12 Gruenenthal Gmbh Tamper-resistant tablet providing immediate drug release
US10300141B2 (en) 2010-09-02 2019-05-28 Grünenthal GmbH Tamper resistant dosage form comprising inorganic salt
US10335373B2 (en) 2012-04-18 2019-07-02 Grunenthal Gmbh Tamper resistant and dose-dumping resistant pharmaceutical dosage form
US10449547B2 (en) 2013-11-26 2019-10-22 Grünenthal GmbH Preparation of a powdery pharmaceutical composition by means of cryo-milling
US10525052B2 (en) 2004-06-12 2020-01-07 Collegium Pharmaceutical, Inc. Abuse-deterrent drug formulations
US10624862B2 (en) 2013-07-12 2020-04-21 Grünenthal GmbH Tamper-resistant dosage form containing ethylene-vinyl acetate polymer
US10632201B2 (en) 2017-10-19 2020-04-28 Capsugel Belgium Nv Immediate release abuse deterrent formulations
US10646485B2 (en) 2016-06-23 2020-05-12 Collegium Pharmaceutical, Inc. Process of making stable abuse-deterrent oral formulations
US10668060B2 (en) 2009-12-10 2020-06-02 Collegium Pharmaceutical, Inc. Tamper-resistant pharmaceutical compositions of opioids and other drugs
US10695297B2 (en) 2011-07-29 2020-06-30 Grünenthal GmbH Tamper-resistant tablet providing immediate drug release
US10842750B2 (en) 2015-09-10 2020-11-24 Grünenthal GmbH Protecting oral overdose with abuse deterrent immediate release formulations
US11478426B2 (en) 2018-09-25 2022-10-25 SpecGx LLC Abuse deterrent immediate release capsule dosage forms
US11517521B2 (en) 2014-07-03 2022-12-06 SpecGx LLC Abuse deterrent immediate release formulations comprising non-cellulose polysaccharides

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102007025858A1 (en) 2007-06-01 2008-12-04 Grünenthal GmbH Process for the preparation of a medicament dosage form
CA2816420C (en) * 2010-10-29 2018-01-16 Najib Babul Compositions of (-)-17-(cyclobutylmethyl)morphinan-3,14-diol
GB201020895D0 (en) * 2010-12-09 2011-01-26 Euro Celtique Sa Dosage form
CA3042642A1 (en) 2013-08-12 2015-02-19 Pharmaceutical Manufacturing Research Services, Inc. Extruded immediate release abuse deterrent pill
US9492444B2 (en) 2013-12-17 2016-11-15 Pharmaceutical Manufacturing Research Services, Inc. Extruded extended release abuse deterrent pill
US10172797B2 (en) 2013-12-17 2019-01-08 Pharmaceutical Manufacturing Research Services, Inc. Extruded extended release abuse deterrent pill
WO2015120201A1 (en) 2014-02-05 2015-08-13 Kashiv Pharma, Llc Abuse-resistant drug formulations with built-in overdose protection
EP3169315B1 (en) 2014-07-17 2020-06-24 Pharmaceutical Manufacturing Research Services, Inc. Immediate release abuse deterrent liquid fill dosage form
US9132096B1 (en) 2014-09-12 2015-09-15 Alkermes Pharma Ireland Limited Abuse resistant pharmaceutical compositions
AU2015336065A1 (en) 2014-10-20 2017-05-04 Pharmaceutical Manufacturing Research Services, Inc. Extended release abuse deterrent liquid fill dosage form
US20170312226A1 (en) * 2016-04-28 2017-11-02 Ascent Pharmaceuticals, Inc. Pharmaceutical dosage forms

Citations (87)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3806603A (en) * 1969-10-13 1974-04-23 W Gaunt Pharmaceutical carriers of plasticized dried milled particles of hydrated cooked rice endosperm
US3865108A (en) * 1971-05-17 1975-02-11 Ortho Pharma Corp Expandable drug delivery device
US3966747A (en) * 1972-10-26 1976-06-29 Bristol-Myers Company 9-Hydroxy-6,7-benzomorphans
US4002173A (en) * 1974-07-23 1977-01-11 International Paper Company Diester crosslinked polyglucan hydrogels and reticulated sponges thereof
US4070497A (en) * 1971-03-09 1978-01-24 Ppg Industries, Inc. Process of applying and curing a plurality of coatings
US4070494A (en) * 1975-07-09 1978-01-24 Bayer Aktiengesellschaft Enteral pharmaceutical compositions
US4200704A (en) * 1978-09-28 1980-04-29 Union Carbide Corporation Controlled degradation of poly(ethylene oxide)
US4262017A (en) * 1978-05-22 1981-04-14 Basf Aktiengesellschaft Preparation of a vitamin E dry powder
US4427681A (en) * 1982-09-16 1984-01-24 Richardson-Vicks, Inc. Thixotropic compositions easily convertible to pourable liquids
US4667013A (en) * 1986-05-02 1987-05-19 Union Carbide Corporation Process for alkylene oxide polymerization
US4744976A (en) * 1984-07-23 1988-05-17 Zetachron, Inc. Erodible matrix for sustained release bioactive composition
US4892889A (en) * 1986-11-18 1990-01-09 Basf Corporation Process for making a spray-dried, directly-compressible vitamin powder comprising unhydrolyzed gelatin
US4892778A (en) * 1987-05-27 1990-01-09 Alza Corporation Juxtaposed laminated arrangement
US4992279A (en) * 1985-07-03 1991-02-12 Kraft General Foods, Inc. Sweetness inhibitor
US4992278A (en) * 1987-01-14 1991-02-12 Ciba-Geigy Corporation Therapeutic system for sparingly soluble active ingredients
US5004601A (en) * 1988-10-14 1991-04-02 Zetachron, Inc. Low-melting moldable pharmaceutical excipient and dosage forms prepared therewith
US5082668A (en) * 1983-05-11 1992-01-21 Alza Corporation Controlled-release system with constant pushing source
US5198226A (en) * 1986-01-30 1993-03-30 Syntex (U.S.A.) Inc. Long acting nicardipine hydrochloride formulation
US5200197A (en) * 1989-11-16 1993-04-06 Alza Corporation Contraceptive pill
US5211892A (en) * 1990-07-20 1993-05-18 L'oreal Process for the compaction of a powder mixture providing an absorbent or partially friable compact product and the product obtained by this process
US5378462A (en) * 1992-08-19 1995-01-03 Kali-Chemie Pharma Gmbh Pancreatin micropellets prepared with polyethylene glycol 4000, paraffin and a lower alcohol by extrusion and rounding
US5508042A (en) * 1991-11-27 1996-04-16 Euro-Celtigue, S.A. Controlled release oxycodone compositions
US5601842A (en) * 1993-09-03 1997-02-11 Gruenenthal Gmbh Sustained release drug formulation containing a tramadol salt
US5620697A (en) * 1992-12-31 1997-04-15 Orion-Yhtyma Oy Method for preparing matrix-type pharmaceutical compositions through ultrasonic means to accomplish melting
US5707636A (en) * 1994-08-03 1998-01-13 Saitec S.R.L. Apparatus and method for preparing solid forms with controlled release of the active ingredient
US5741519A (en) * 1995-03-21 1998-04-21 Basf Aktiengesellschaft The production of active substance compositions in the form of a solid solution of the active substance in a polymer matrix, and active substance compositions produced by this process
US5866164A (en) * 1996-03-12 1999-02-02 Alza Corporation Composition and dosage form comprising opioid antagonist
US6009690A (en) * 1994-12-23 2000-01-04 Basf Aktiengesellschaft Process and apparatus for the production of divisible tablets
US6235825B1 (en) * 1998-03-05 2001-05-22 Mitsui Chemicals, Inc. Polylactic acid resin composition and film therefrom
US6238697B1 (en) * 1998-12-21 2001-05-29 Pharmalogix, Inc. Methods and formulations for making bupropion hydrochloride tablets using direct compression
US6340475B2 (en) * 1997-06-06 2002-01-22 Depomed, Inc. Extending the duration of drug release within the stomach during the fed mode
US20020012701A1 (en) * 2000-06-19 2002-01-31 Karl Kolter Process for producing solid oral dosage forms with sustained release of active ingredient
US6344535B1 (en) * 1997-12-03 2002-02-05 Bayer Aktiengesellschaft Polyether ester amides
US20020015730A1 (en) * 2000-03-09 2002-02-07 Torsten Hoffmann Pharmaceutical formulations and method for making
US6348469B1 (en) * 1995-04-14 2002-02-19 Pharma Pass Llc Solid compositions containing glipizide and polyethylene oxide
US6355656B1 (en) * 1995-12-04 2002-03-12 Celgene Corporation Phenidate drug formulations having diminished abuse potential
US6375963B1 (en) * 1999-06-16 2002-04-23 Michael A. Repka Bioadhesive hot-melt extruded film for topical and mucosal adhesion applications and drug delivery and process for preparation thereof
US6375957B1 (en) * 1997-12-22 2002-04-23 Euro-Celtique, S.A. Opioid agonist/opioid antagonist/acetaminophen combinations
US20030008409A1 (en) * 2001-07-03 2003-01-09 Spearman Steven R. Method and apparatus for determining sunlight exposure
US20030021546A1 (en) * 2001-07-30 2003-01-30 Tsuguo Sato Optical fiber ferrule assembly and optical module and optical connector using the same
US20030044464A1 (en) * 1999-08-31 2003-03-06 Iris Ziegler Sustained-release, oral pharamaceutical forms of formulation
US20030044458A1 (en) * 2001-08-06 2003-03-06 Curtis Wright Oral dosage form comprising a therapeutic agent and an adverse-effect agent
US6534089B1 (en) * 1996-04-05 2003-03-18 Alza Corporation Uniform drug delivery therapy
US20030064099A1 (en) * 2001-08-06 2003-04-03 Benjamin Oshlack Pharmaceutical formulation containing bittering agent
US20030068375A1 (en) * 2001-08-06 2003-04-10 Curtis Wright Pharmaceutical formulation containing gelling agent
US20030069263A1 (en) * 2001-07-18 2003-04-10 Breder Christopher D. Pharmaceutical combinations of oxycodone and naloxone
US20030068276A1 (en) * 2001-09-17 2003-04-10 Lyn Hughes Dosage forms
US20030068392A1 (en) * 2001-08-06 2003-04-10 Richard Sackler Pharmaceutical formulation containing opioid agonist, opioid antagonist and irritant
US20030068371A1 (en) * 2001-08-06 2003-04-10 Benjamin Oshlack Pharmaceutical formulation containing opioid agonist,opioid antagonist and gelling agent
US20030068370A1 (en) * 2001-08-06 2003-04-10 Richard Sackler Pharmaceutical formulation containing irritant
US6547997B1 (en) * 1997-11-28 2003-04-15 Abbot Laboratories Method for producing solvent-free noncrystalline biologically active substances
US6562375B1 (en) * 1999-08-04 2003-05-13 Yamanouchi Pharmaceuticals, Co., Ltd. Stable pharmaceutical composition for oral use
US20030091630A1 (en) * 2001-10-25 2003-05-15 Jenny Louie-Helm Formulation of an erodible, gastric retentive oral dosage form using in vitro disintegration test data
US20040010000A1 (en) * 2002-04-29 2004-01-15 Ayer Atul D. Methods and dosage forms for controlled delivery of oxycodone
US6699503B1 (en) * 1992-09-18 2004-03-02 Yamanuchi Pharmaceutical Co., Ltd. Hydrogel-forming sustained-release preparation
US20040052844A1 (en) * 2002-09-16 2004-03-18 Fang-Hsiung Hsiao Time-controlled, sustained release, pharmaceutical composition containing water-soluble resins
US20040052731A1 (en) * 2002-07-05 2004-03-18 Collegium Pharmaceuticals, Inc. Abuse-deterrent pharmaceutical compositions of opiods and other drugs
US6723340B2 (en) * 2001-10-25 2004-04-20 Depomed, Inc. Optimal polymer mixtures for gastric retentive tablets
US20040081694A1 (en) * 1994-11-04 2004-04-29 Euro-Celtique, S.A. Melt-extruded orally administrable opioid formulations
US6733783B2 (en) * 2000-10-30 2004-05-11 Euro-Celtique S.A. Controlled release hydrocodone formulations
US20040091528A1 (en) * 2002-11-12 2004-05-13 Yamanouchi Pharma Technologies, Inc. Soluble drug extended release system
US20050031546A1 (en) * 2003-08-06 2005-02-10 Johannes Bartholomaus Abuse-proffed dosage form
US20050058706A1 (en) * 2001-10-24 2005-03-17 Grunenthal Gmbh Delayed release pharmaceutical composition containing 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol
US20050095291A1 (en) * 2000-02-08 2005-05-05 Benjamin Oshlack Tamper-resistant oral opioid agonist formulations
US20050106249A1 (en) * 2002-04-29 2005-05-19 Stephen Hwang Once-a-day, oral, controlled-release, oxycodone dosage forms
US20050112067A1 (en) * 2003-11-26 2005-05-26 Vijai Kumar Methods and compositions for deterring abuse of opioid containing dosage forms
US20060002859A1 (en) * 2004-07-01 2006-01-05 Elisabeth Arkenau Process for production of an abuse-proofed solid dosage form
US20060039864A1 (en) * 2004-07-01 2006-02-23 Johannes Bartholomaus Abuse-proofed oral dosage form
US20060064009A1 (en) * 2004-09-21 2006-03-23 Webler William E Vessel imaging devices and methods
US20070020335A1 (en) * 2005-07-07 2007-01-25 Farnam Companies, Inc. Sustained release pharmaceutical compositions for highly water soluble drugs
US7176251B1 (en) * 1996-11-05 2007-02-13 Novamont S.P.A. Biodegradable polymeric compositions comprising starch and a thermoplastic polymer
US20070048228A1 (en) * 2003-08-06 2007-03-01 Elisabeth Arkenau-Maric Abuse-proofed dosage form
US20070065365A1 (en) * 2004-04-21 2007-03-22 Gruenenthal Gmbh Abuse-resistant transdermal system
US20070092573A1 (en) * 2005-10-24 2007-04-26 Laxminarayan Joshi Stabilized extended release pharmaceutical compositions comprising a beta-adrenoreceptor antagonist
US7214385B2 (en) * 2001-08-06 2007-05-08 Thomas J. Gruber Pharmaceutical formulation containing dye
US20080069871A1 (en) * 2006-07-21 2008-03-20 Vaughn Jason M Hydrophobic abuse deterrent delivery system
US20090004267A1 (en) * 2007-03-07 2009-01-01 Gruenenthal Gmbh Dosage Form with Impeded Abuse
US20090017121A1 (en) * 2001-10-25 2009-01-15 Bret Berner Gastric retained gabapentin dosage form
US7674800B2 (en) * 2004-03-30 2010-03-09 Purdue Pharma L.P. Oxycodone hydrochloride having less than 25 PPM 14-hydroxycodeinone
US20100092553A1 (en) * 2005-11-10 2010-04-15 Flamel Technologies anti-misuse microparticulate oral pharmaceutical form
US20100098758A1 (en) * 2002-10-25 2010-04-22 Gruenenthal Gmbh Abuse-Resistant Dosage Form
US20110020451A1 (en) * 2009-07-22 2011-01-27 Grunenthal Gmbh Tamper-resistant dosage form for oxidation-sensitive opioids
US20110020454A1 (en) * 2008-03-13 2011-01-27 Rosa Lamarca Casado Novel dosage and formulation
US20110038930A1 (en) * 2009-07-22 2011-02-17 Grunenthal Gmbh Hot-melt extruded pharmaceutical dosage form
US20110082214A1 (en) * 2008-05-09 2011-04-07 Gruenthal Gmbh Process for the preparation of a solid dosage form, in particular a tablet, for pharmaceutical use and process for the preparation of a precursor for a solid dosage form, in particular a tablet
US7939543B2 (en) * 2005-03-04 2011-05-10 Purdue Pharma L.P. Method of reducing α, β unsaturated ketones in opioid compositions
US8114838B2 (en) * 2000-05-23 2012-02-14 Acorda Therapeutics, Inc. Methods for protecting dopaminergic neurons from stress and promoting proliferation and differentiation of oligodendrocyte progenitors by NRG-2

Family Cites Families (494)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2524855A (en) 1950-10-10 Process for the manufacture of
CA722109A (en) 1965-11-23 W. Mock Henry Extrusion of ethylene oxide polymers
US2806033A (en) 1955-08-03 1957-09-10 Lewenstein Morphine derivative
US2987445A (en) 1958-10-10 1961-06-06 Rohm & Haas Drug composition
US3370035A (en) 1961-06-23 1968-02-20 Takeda Chemical Industries Ltd Stabilization of polyalkylene oxide
US3332950A (en) 1963-03-23 1967-07-25 Endo Lab 14-hydroxydihydronormorphinone derivatives
GB1147210A (en) 1965-06-30 1969-04-02 Eastman Kodak Co Improvements in or relating to vitamins
US3652589A (en) 1967-07-27 1972-03-28 Gruenenthal Chemie 1-(m-substituted phenyl)-2-aminomethyl cyclohexanols
CH503520A (en) 1969-12-15 1971-02-28 Inventa Ag Process for grinding granular materials, in particular plastic granulates, at low temperatures
US4014965A (en) * 1972-11-24 1977-03-29 The Dow Chemical Company Process for scrapless forming of plastic articles
US3980766A (en) 1973-08-13 1976-09-14 West Laboratories, Inc. Orally administered drug composition for therapy in the treatment of narcotic drug addiction
US3941865A (en) * 1973-12-10 1976-03-02 Union Carbide Corporation Extrusion of ethylene oxide resins
JPS603286B2 (en) 1977-03-03 1985-01-26 日本化薬株式会社 Constant-dissolution formulation
US4207893A (en) * 1977-08-29 1980-06-17 Alza Corporation Device using hydrophilic polymer for delivering drug to biological environment
US4175119A (en) 1978-01-11 1979-11-20 Porter Garry L Composition and method to prevent accidental and intentional overdosage with psychoactive drugs
US4211681A (en) 1978-08-16 1980-07-08 Union Carbide Corporation Poly(ethylene oxide) compositions
NO793297L (en) 1978-10-19 1980-04-22 Mallinckrodt Inc PROCEDURE FOR THE MANUFACTURE OF OXYMORPHONE
US4258027A (en) 1979-03-26 1981-03-24 Mead Johnson & Company Multi-fractionable tablet structure
US4215104A (en) 1979-03-26 1980-07-29 Mead Johnson & Company Multi-fractionable tablet structure
CA1146866A (en) 1979-07-05 1983-05-24 Yamanouchi Pharmaceutical Co. Ltd. Process for the production of sustained release pharmaceutical composition of solid medical material
US4353887A (en) 1979-08-16 1982-10-12 Ciba-Geigy Corporation Divisible tablet having controlled and delayed release of the active substance
CH648754A5 (en) 1979-08-16 1985-04-15 Ciba Geigy Ag Pharmaceutical slow release tablet
US4457933A (en) * 1980-01-24 1984-07-03 Bristol-Myers Company Prevention of analgesic abuse
JPS56169622A (en) 1980-06-03 1981-12-26 Kissei Pharmaceut Co Ltd Method of making solid preparation from oily substance
DE3024416C2 (en) 1980-06-28 1982-04-15 Gödecke AG, 1000 Berlin Process for the production of medicaments with sustained release of active substances
US4473640A (en) 1982-06-03 1984-09-25 Combie Joan D Detection of morphine and its analogues using enzymatic hydrolysis
US4462941A (en) 1982-06-10 1984-07-31 The Regents Of The University Of California Dynorphin amide analogs
US4427778A (en) 1982-06-29 1984-01-24 Biochem Technology, Inc. Enzymatic preparation of particulate cellulose for tablet making
US4485211A (en) 1982-09-15 1984-11-27 The B. F. Goodrich Company Poly(glycidyl ether)block copolymers and process for their preparation
US4529583A (en) 1983-03-07 1985-07-16 Clear Lake Development Group Composition and method of immobilizing emetics and method of treating human beings with emetics
US4603143A (en) 1983-05-02 1986-07-29 Basf Corporation Free-flowing, high density, fat soluble vitamin powders with improved stability
US4765989A (en) 1983-05-11 1988-08-23 Alza Corporation Osmotic device for administering certain drugs
US4612008A (en) 1983-05-11 1986-09-16 Alza Corporation Osmotic device with dual thermodynamic activity
US4783337A (en) 1983-05-11 1988-11-08 Alza Corporation Osmotic system comprising plurality of members for dispensing drug
US4599342A (en) * 1984-01-16 1986-07-08 The Procter & Gamble Company Pharmaceutical products providing enhanced analgesia
AU592065B2 (en) 1984-10-09 1990-01-04 Dow Chemical Company, The Sustained release dosage form based on highly plasticized cellulose ether gels
GB8507779D0 (en) 1985-03-26 1985-05-01 Fujisawa Pharmaceutical Co Drug carrier
EP0228417B1 (en) 1985-06-24 1990-08-29 Ici Australia Limited Ingestible capsules
DE3689195T2 (en) 1985-06-28 1994-05-05 Carrington Lab Inc Process for the production of aloe products, products and compositions therefor.
US4851521A (en) 1985-07-08 1989-07-25 Fidia, S.P.A. Esters of hyaluronic acid
EP0226061B1 (en) 1985-12-17 1994-02-16 United States Surgical Corporation High molecular weight bioresorbable polymers and implantation devices thereof
US5229164A (en) 1985-12-19 1993-07-20 Capsoid Pharma Gmbh Process for producing individually dosed administration forms
US4711894A (en) 1986-01-16 1987-12-08 Henkel Corporation Stabilized tocopherol in dry, particulate, free-flowing form
US4940556A (en) 1986-01-30 1990-07-10 Syntex (U.S.A.) Inc. Method of preparing long acting formulation
US4764378A (en) 1986-02-10 1988-08-16 Zetachron, Inc. Buccal drug dosage form
EP0239973A3 (en) 1986-03-31 1989-11-08 Union Carbide Corporation Catalyst and process for alkylene oxide polymerization
DE3612211A1 (en) 1986-04-11 1987-10-15 Basf Ag CONTINUOUS TABLET METHOD
US4713243A (en) 1986-06-16 1987-12-15 Johnson & Johnson Products, Inc. Bioadhesive extruded film for intra-oral drug delivery and process
USRE33093E (en) 1986-06-16 1989-10-17 Johnson & Johnson Consumer Products, Inc. Bioadhesive extruded film for intra-oral drug delivery and process
USRE34990E (en) 1986-08-07 1995-07-04 Ciba-Geigy Corporation Oral therapeutic system having systemic action
CA1335748C (en) 1986-09-25 1995-05-30 Jeffrey Lawrence Finnan Crosslinked gelatins
US5227157A (en) * 1986-10-14 1993-07-13 Board Of Regents, The University Of Texas System Delivery of therapeutic agents
EP0277289B8 (en) 1986-11-10 2003-05-21 Biopure Corporation Extra pure semi-synthetic blood substitute
JPH0831303B2 (en) 1986-12-01 1996-03-27 オムロン株式会社 Chip type fuse
US5051261A (en) 1987-11-24 1991-09-24 Fmc Corporation Method for preparing a solid sustained release form of a functionally active composition
KR900700071A (en) 1987-12-17 1990-08-11 로버어트 에이 아미테이지 Tri-scored Drug Tablets
DE3812567A1 (en) 1988-04-15 1989-10-26 Basf Ag METHOD FOR PRODUCING PHARMACEUTICAL MIXTURES
US4954346A (en) 1988-06-08 1990-09-04 Ciba-Geigy Corporation Orally administrable nifedipine solution in a solid light resistant dosage form
US4960814A (en) 1988-06-13 1990-10-02 Eastman Kodak Company Water-dispersible polymeric compositions
US5350741A (en) 1988-07-30 1994-09-27 Kanji Takada Enteric formulations of physiologically active peptides and proteins
JPH0249719A (en) 1988-08-11 1990-02-20 Dai Ichi Kogyo Seiyaku Co Ltd Oil soluble-vitamin powder having readily water-dispersible and soluble performance
GB8820327D0 (en) 1988-08-26 1988-09-28 May & Baker Ltd New compositions of matter
DE3830353A1 (en) 1988-09-07 1990-03-15 Basf Ag METHOD FOR THE CONTINUOUS PRODUCTION OF SOLID PHARMACEUTICAL FORMS
US5139790A (en) 1988-10-14 1992-08-18 Zetachron, Inc. Low-melting moldable pharmaceutical excipient and dosage forms prepared therewith
US4957668A (en) 1988-12-07 1990-09-18 General Motors Corporation Ultrasonic compacting and bonding particles
US5190760A (en) 1989-07-08 1993-03-02 Coopers Animal Health Limited Solid pharmaceutical composition
US5169645A (en) 1989-10-31 1992-12-08 Duquesne University Of The Holy Ghost Directly compressible granules having improved flow properties
GB8926612D0 (en) 1989-11-24 1990-01-17 Erba Farmitalia Pharmaceutical compositions
EP0449775A3 (en) 1990-03-29 1992-09-02 Ciba-Geigy Ag Polyether-polyester block copolymers and their use as dispersing agents
EP0477135A1 (en) 1990-09-07 1992-03-25 Warner-Lambert Company Chewable spheroidal coated microcapsules and methods for preparing same
US5126151A (en) * 1991-01-24 1992-06-30 Warner-Lambert Company Encapsulation matrix
EP0500091B1 (en) * 1991-02-20 1998-07-15 Hitachi, Ltd. Television telephone
US5273758A (en) 1991-03-18 1993-12-28 Sandoz Ltd. Directly compressible polyethylene oxide vehicle for preparing therapeutic dosage forms
US5149538A (en) 1991-06-14 1992-09-22 Warner-Lambert Company Misuse-resistive transdermal opioid dosage form
JP3073054B2 (en) 1991-07-11 2000-08-07 住友精化株式会社 Method for producing alkylene oxide polymer
DK0662320T3 (en) 1991-08-30 2001-09-24 Showa Pharm Chem Ind Dry gel composition
WO1993006723A1 (en) * 1991-10-04 1993-04-15 Olin Corporation Fungicide tablet
DE69229881T2 (en) 1991-10-04 1999-12-09 Yoshitomi Pharmaceutical DELAYED RELEASE TABLET
DE4138513A1 (en) 1991-11-23 1993-05-27 Basf Ag SOLID PHARMACEUTICAL RETARD FORM
WO1993010758A1 (en) 1991-12-05 1993-06-10 Pitman-Moore, Inc. A carbohydrate glass matrix for the sustained release of a therapeutic agent
US5200194A (en) 1991-12-18 1993-04-06 Alza Corporation Oral osmotic device
JP3722293B2 (en) 1991-12-18 2005-11-30 ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー Novel pharmaceutical solid dispersion
US5225417A (en) 1992-01-21 1993-07-06 G. D. Searle & Co. Opioid agonist compounds
IL105553A (en) 1992-05-06 1998-01-04 Janssen Pharmaceutica Inc Solid dosage form comprising a porous network of matrix forming material which disperses rapidly in water
DE59302200D1 (en) 1992-05-22 1996-05-15 Goedecke Ag METHOD FOR PRODUCING RETARDED DRUG PREPARATIONS
GB9217295D0 (en) 1992-08-14 1992-09-30 Wellcome Found Controlled released tablets
DE4229085C2 (en) 1992-09-01 1996-07-11 Boehringer Mannheim Gmbh Elongated, divisible tablet
US5472943A (en) 1992-09-21 1995-12-05 Albert Einstein College Of Medicine Of Yeshiva University, Method of simultaneously enhancing analgesic potency and attenuating dependence liability caused by morphine and other opioid agonists
FI101039B (en) 1992-10-09 1998-04-15 Eeva Kristoffersson Method for preparing medicated pellets
AU679937B2 (en) 1992-11-18 1997-07-17 Johnson & Johnson Consumer Products, Inc. Extrudable compositions for topical or transdermal drug delivery
ATE183641T1 (en) 1992-12-23 1999-09-15 Saitec Srl METHOD FOR PRODUCING MEDICINAL FORMS AND CONTROLLED RELEASE AND THE MEDICINAL FORMS OBTAINED
US6071970A (en) 1993-02-08 2000-06-06 Nps Pharmaceuticals, Inc. Compounds active at a novel site on receptor-operated calcium channels useful for treatment of neurological disorders and diseases
US5914132A (en) 1993-02-26 1999-06-22 The Procter & Gamble Company Pharmaceutical dosage form with multiple enteric polymer coatings for colonic delivery
DE4309528C2 (en) 1993-03-24 1998-05-20 Doxa Gmbh Casein film or film tube, process for their production and their use
IL119660A (en) 1993-05-10 2002-09-12 Euro Celtique Sa Controlled release formulation comprising tramadol
IL109944A (en) 1993-07-01 1998-12-06 Euro Celtique Sa Sustained release dosage unit forms containing morphine and a method of preparing these sustained release dosage unit forms
EP1442745A1 (en) 1993-10-07 2004-08-04 Euro-Celtique Orally administrable opioid formulations having extended duration of effect
KR100354702B1 (en) 1993-11-23 2002-12-28 유로-셀티크 소시에떼 아노뉨 Manufacturing method and sustained release composition of pharmaceutical composition
ES2168290T3 (en) 1993-11-23 2002-06-16 Euro Celtique Sa METHOD FOR PREPARING A SUSTAINED RELEASE COMPOSITION.
AU1266895A (en) 1993-12-20 1995-07-10 Procter & Gamble Company, The Process for making laxatives containing dioctyl sulfosuccinate
IL112106A0 (en) 1993-12-22 1995-03-15 Ergo Science Inc Accelerated release composition containing bromocriptine
GB9401894D0 (en) 1994-02-01 1994-03-30 Rhone Poulenc Rorer Ltd New compositions of matter
EP0744941B1 (en) 1994-02-16 2003-06-04 Abbott Laboratories Process for preparing fine particle pharmaceutical formulations
SE9503924D0 (en) 1995-08-18 1995-11-07 Astra Ab Novel opioid peptides
US5458887A (en) 1994-03-02 1995-10-17 Andrx Pharmaceuticals, Inc. Controlled release tablet formulation
DE4413350A1 (en) 1994-04-18 1995-10-19 Basf Ag Retard matrix pellets and process for their production
SI9520049A (en) 1994-05-06 1997-12-31 Pfizer Controlled-release dosage forms of azithromycin
AT403988B (en) * 1994-05-18 1998-07-27 Lannacher Heilmittel SOLID ORAL RETARDED PREPARATION
US5460826A (en) 1994-06-27 1995-10-24 Alza Corporation Morphine therapy
DE4426245A1 (en) 1994-07-23 1996-02-22 Gruenenthal Gmbh 1-phenyl-3-dimethylamino-propane compounds with pharmacological activity
US5837790A (en) 1994-10-24 1998-11-17 Amcol International Corporation Precipitation polymerization process for producing an oil adsorbent polymer capable of entrapping solid particles and liquids and the product thereof
AUPM897594A0 (en) 1994-10-25 1994-11-17 Daratech Pty Ltd Controlled release container
DE19504832A1 (en) 1995-02-14 1996-08-22 Basf Ag Solid drug preparations
US5945125A (en) 1995-02-28 1999-08-31 Temple University Controlled release tablet
US6117453A (en) 1995-04-14 2000-09-12 Pharma Pass Solid compositions containing polyethylene oxide and an active ingredient
US5900425A (en) 1995-05-02 1999-05-04 Bayer Aktiengesellschaft Pharmaceutical preparations having controlled release of active compound and processes for their preparation
DE19522899C1 (en) 1995-06-23 1996-12-19 Hexal Pharmaforschung Gmbh Process for the continuous sintering of a granulate
US5759583A (en) 1995-08-30 1998-06-02 Syntex (U.S.A.) Inc. Sustained release poly (lactic/glycolic) matrices
US6063405A (en) 1995-09-29 2000-05-16 L.A.M. Pharmaceuticals, Llc Sustained release delivery system
US5811126A (en) 1995-10-02 1998-09-22 Euro-Celtique, S.A. Controlled release matrix for pharmaceuticals
DE19539361A1 (en) 1995-10-23 1997-04-24 Basf Ag Process for the preparation of multilayer, solid pharmaceutical forms for oral or rectal administration
US5908850A (en) * 1995-12-04 1999-06-01 Celgene Corporation Method of treating attention deficit disorders with d-threo methylphenidate
DE19547766A1 (en) 1995-12-20 1997-06-26 Gruenenthal Gmbh 1-phenyl-2-dimethylaminomethyl-cyclohexan-1-ol compounds as active pharmaceutical ingredients
US6461644B1 (en) 1996-03-25 2002-10-08 Richard R. Jackson Anesthetizing plastics, drug delivery plastics, and related medical products, systems and methods
US20020114838A1 (en) 1996-04-05 2002-08-22 Ayer Atul D. Uniform drug delivery therapy
DE69713890T3 (en) 1996-04-05 2006-09-07 Takeda Pharmaceutical Co. Ltd. PHARMACEUTICAL COMBINATION CONTAINING AN ACTIVE AGENT WITH ANGIOTENSIN-II ANTAGONISTIC ACTIVITY AND AN ACTIVE SUBSTANCE THAT INCREASES INSULIN SENSITIVITY
US5817343A (en) 1996-05-14 1998-10-06 Alkermes, Inc. Method for fabricating polymer-based controlled-release devices
IL127378A (en) 1996-06-06 2003-07-31 Bifodan As Enteric coating for an oral preparation
AU3508097A (en) * 1996-06-26 1998-01-14 Board Of Regents, The University Of Texas System Hot-melt extrudable pharmaceutical formulation
WO1998001117A1 (en) 1996-07-08 1998-01-15 Edward Mendell Co., Inc. Sustained release matrix for high-dose insoluble drugs
DE19629753A1 (en) 1996-07-23 1998-01-29 Basf Ag Process for the production of solid dosage forms
NL1003684C2 (en) 1996-07-25 1998-01-28 Weterings B V H Device for dispensing a liquid.
DE19630236A1 (en) 1996-07-26 1998-01-29 Wolff Walsrode Ag Biaxially stretched, biodegradable and compostable sausage casing
BE1010353A5 (en) 1996-08-14 1998-06-02 Boss Pharmaceuticals Ag Method for manufacture of pharmaceutical products, device for such a method and pharmaceutical products obtained.
US5991799A (en) 1996-12-20 1999-11-23 Liberate Technologies Information retrieval system using an internet multiplexer to focus user selection
DE19705538C1 (en) 1997-02-14 1998-08-27 Goedecke Ag Process for the separation of active substances in solid pharmaceutical preparations
US5948787A (en) * 1997-02-28 1999-09-07 Alza Corporation Compositions containing opiate analgesics
DE19710009A1 (en) 1997-03-12 1998-09-24 Knoll Ag Multi-phase preparation forms containing active ingredients
DE19710213A1 (en) 1997-03-12 1998-09-17 Basf Ag Process for the manufacture of solid combination dosage forms
DE19710008A1 (en) 1997-03-12 1998-09-17 Basf Ag Solid, at least two-phase formulations of a sustained-release opioid analgesic
US6139770A (en) 1997-05-16 2000-10-31 Chevron Chemical Company Llc Photoinitiators and oxygen scavenging compositions
DE19721467A1 (en) 1997-05-22 1998-11-26 Basf Ag Process for the preparation of small-scale preparations of biologically active substances
US6635280B2 (en) 1997-06-06 2003-10-21 Depomed, Inc. Extending the duration of drug release within the stomach during the fed mode
PT1009387E (en) 1997-07-02 2006-08-31 Euro Celtique Sa STABILIZED CONTROLLED FREQUENCY FORMULATIONS OF TRAMADOL
IE970588A1 (en) * 1997-08-01 2000-08-23 Elan Corp Plc Controlled release pharmaceutical compositions containing tiagabine
JP2003525828A (en) 1997-09-10 2003-09-02 アライドシグナル インコーポレイテッド Injection molding of zirconia-based structural materials by wet method
US6009390A (en) 1997-09-11 1999-12-28 Lucent Technologies Inc. Technique for selective use of Gaussian kernels and mixture component weights of tied-mixture hidden Markov models for speech recognition
DE19753534A1 (en) 1997-12-03 1999-06-10 Bayer Ag Biodegradable thermoplastic polyester-amides with good mechanical properties for molding, film and fiber, useful for e.g. compostable refuse bag
CN1204890C (en) 1997-12-22 2005-06-08 欧罗赛铁克股份有限公司 Method for preventing abuse of opioid dosage forms
DE19800689C1 (en) 1998-01-10 1999-07-15 Deloro Stellite Gmbh Shaped body made of a wear-resistant material
DE19800698A1 (en) 1998-01-10 1999-07-15 Bayer Ag Biodegradable polyester amides with block-like polyester and polyamide segments
US6251430B1 (en) 1998-02-04 2001-06-26 Guohua Zhang Water insoluble polymer based sustained release formulation
AU2587299A (en) 1998-02-06 1999-08-23 Union Carbide Chemicals & Plastics Technology Corporation Alkylene oxide polymer compositions
US6245357B1 (en) 1998-03-06 2001-06-12 Alza Corporation Extended release dosage form
US6090411A (en) 1998-03-09 2000-07-18 Temple University Monolithic tablet for controlled drug release
US6110500A (en) 1998-03-25 2000-08-29 Temple University Coated tablet with long term parabolic and zero-order release kinetics
KR20010042419A (en) 1998-04-02 2001-05-25 조셉 제이. 스위니 Method for etching low k dielectrics
JP4533531B2 (en) 1998-04-03 2010-09-01 ビーエム リサーチ エイ／エス Controlled release composition
US5962488A (en) 1998-04-08 1999-10-05 Roberts Laboratories, Inc. Stable pharmaceutical formulations for treating internal bowel syndrome containing isoxazole derivatives
DE19822979A1 (en) 1998-05-25 1999-12-02 Kalle Nalo Gmbh & Co Kg Film with starch or starch derivatives and polyester urethanes and process for their production
US6333087B1 (en) * 1998-08-27 2001-12-25 Chevron Chemical Company Llc Oxygen scavenging packaging
DE19841244A1 (en) 1998-09-09 2000-03-16 Knoll Ag Method and device for making tablets
GT199900148A (en) 1998-09-10 2001-02-28 Denaturing for the sympathomimetic amine salts.
US6268177B1 (en) 1998-09-22 2001-07-31 Smithkline Beecham Corporation Isolated nucleic acid encoding nucleotide pyrophosphorylase
CN1327384A (en) 1998-10-20 2001-12-19 韩国科学技术研究院 Bioflavonoids as plasma high density lipoprotein level increasing agent
US20010055613A1 (en) 1998-10-21 2001-12-27 Beth A. Burnside Oral pulsed dose drug delivery system
US20060240105A1 (en) 1998-11-02 2006-10-26 Elan Corporation, Plc Multiparticulate modified release composition
ES2141688B1 (en) 1998-11-06 2001-02-01 Vita Invest Sa NEW ESTERS DERIVED FROM SUBSTITUTED FENIL-CICLOHEXIL COMPOUNDS.
DE19855440A1 (en) 1998-12-01 2000-06-08 Basf Ag Process for the production of solid dosage forms by melt extrusion
EP1005863A1 (en) 1998-12-04 2000-06-07 Synthelabo Controlled-release dosage forms comprising a short acting hypnotic or a salt thereof
DE19856147A1 (en) 1998-12-04 2000-06-08 Knoll Ag Divisible solid dosage forms and methods for their preparation
US6419960B1 (en) * 1998-12-17 2002-07-16 Euro-Celtique S.A. Controlled release formulations having rapid onset and rapid decline of effective plasma drug concentrations
WO2000040205A2 (en) * 1999-01-05 2000-07-13 Copley Pharmaceutical Inc. Sustained release formulation with reduced moisture sensitivity
CA2321107A1 (en) 1999-02-04 2000-08-10 Nichimo Co., Ltd. Materials for preventing arteriosclerosis, immunopotentiating materials, vertebrates fed with these materials and eggs thereof
US7374779B2 (en) 1999-02-26 2008-05-20 Lipocine, Inc. Pharmaceutical formulations and systems for improved absorption and multistage release of active agents
US6384020B1 (en) 1999-07-14 2002-05-07 Shire Laboratories, Inc. Rapid immediate release oral dosage form
US20030118641A1 (en) * 2000-07-27 2003-06-26 Roxane Laboratories, Inc. Abuse-resistant sustained-release opioid formulation
AU6381300A (en) * 1999-07-29 2001-02-19 Roxane Laboratories, Inc. Opioid sustained-released formulation
ATE324909T1 (en) 1999-08-04 2006-06-15 Astellas Pharma Inc STABLE MEDICAL COMPOSITIONS FOR ORAL ADMINISTRATION USING IRON OXIDES
KR100345214B1 (en) 1999-08-17 2002-07-25 이강춘 The nasal transmucosal delivery of peptides conjugated with biocompatible polymers
DE19940740A1 (en) * 1999-08-31 2001-03-01 Gruenenthal Gmbh Pharmaceutical salts
CA2388560A1 (en) * 1999-08-31 2001-03-08 Grunenthal Gmbh Sustained-release form of administration containing tramadol saccharinate
DE19960494A1 (en) 1999-12-15 2001-06-21 Knoll Ag Device and method for producing solid active substance-containing forms
ES2160534B1 (en) 1999-12-30 2002-04-16 Vita Invest Sa NEW ESTERS DERIVED FROM (RR, SS) -2-HYDROXIBENZOATE 3- (2-DIMETHYLMINOME-1-HYDROXICICLOHEXIL) PHENYL.
US6680070B1 (en) 2000-01-18 2004-01-20 Albemarle Corporation Particulate blends and compacted products formed therefrom, and the preparation thereof
DE10015479A1 (en) 2000-03-29 2001-10-11 Basf Ag Solid oral dosage forms with delayed release of active ingredient and high mechanical stability
US8012504B2 (en) 2000-04-28 2011-09-06 Reckitt Benckiser Inc. Sustained release of guaifenesin combination drugs
US6572887B2 (en) 2000-05-01 2003-06-03 National Starch And Chemical Investment Holding Corporation Polysaccharide material for direct compression
US6419954B1 (en) 2000-05-19 2002-07-16 Yamanouchi Pharmaceutical Co., Ltd. Tablets and methods for modified release of hydrophilic and other active agents
US6488962B1 (en) 2000-06-20 2002-12-03 Depomed, Inc. Tablet shapes to enhance gastric retention of swellable controlled-release oral dosage forms
US6607748B1 (en) 2000-06-29 2003-08-19 Vincent Lenaerts Cross-linked high amylose starch for use in controlled-release pharmaceutical formulations and processes for its manufacture
DE10036400A1 (en) 2000-07-26 2002-06-06 Mitsubishi Polyester Film Gmbh White, biaxially oriented polyester film
WO2002026262A2 (en) 2000-09-25 2002-04-04 Pro-Pharmaceuticals, Inc. Compositions for reducing side effects in chemotherapeutic treatments
NZ523687A (en) 2000-09-27 2005-03-24 Danisco Antimicrobial agent
WO2002026928A1 (en) 2000-09-28 2002-04-04 The Dow Chemical Company Polymer composite structures useful for controlled release systems
GB0026137D0 (en) 2000-10-25 2000-12-13 Euro Celtique Sa Transdermal dosage form
US6344215B1 (en) 2000-10-27 2002-02-05 Eurand America, Inc. Methylphenidate modified release formulations
AU2002226098A1 (en) 2000-10-30 2002-05-15 The Board Of Regents, The University Of Texas System Spherical particles produced by a hot-melt extrusion/spheronization process
DE10109763A1 (en) 2001-02-28 2002-09-05 Gruenenthal Gmbh Pharmaceutical salts
JP2002265592A (en) 2001-03-07 2002-09-18 Sumitomo Seika Chem Co Ltd Process for producing alkylene oxide polymer
WO2002071860A1 (en) 2001-03-13 2002-09-19 L.A. Dreyfus Co. Gum base and gum manufacturing using particulated gum base ingredients
JP3967554B2 (en) 2001-03-15 2007-08-29 株式会社ポッカコーポレーション Flavonoid compound and method for producing the same
US20020132395A1 (en) 2001-03-16 2002-09-19 International Business Machines Corporation Body contact in SOI devices by electrically weakening the oxide under the body
EP1241110A1 (en) 2001-03-16 2002-09-18 Pfizer Products Inc. Dispensing unit for oxygen-sensitive drugs
EP1385486A4 (en) 2001-04-18 2006-05-17 Nostrum Pharmaceuticals Inc A novel coating for a sustained release pharmaceutical composition
US20020187192A1 (en) 2001-04-30 2002-12-12 Yatindra Joshi Pharmaceutical composition which reduces or eliminates drug abuse potential
EP1385898B1 (en) 2001-05-01 2006-05-31 Union Carbide Chemicals & Plastics Technology Corporation Pharmaceutical composition comprising poly(alkylene oxides) having reduced amounts of formic compounds
UA81224C2 (en) 2001-05-02 2007-12-25 Euro Celtic S A Dosage form of oxycodone and use thereof
WO2002090316A1 (en) 2001-05-08 2002-11-14 The Johns Hopkins University Method of inhibiting methamphetamine synthesis
US20030004177A1 (en) * 2001-05-11 2003-01-02 Endo Pharmaceuticals, Inc. Abuse-resistant opioid dosage form
CN1525851A (en) 2001-05-11 2004-09-01 ������ҩ�����޹�˾ Abuse-resistant controlled-release opioid dosage form
US6623754B2 (en) 2001-05-21 2003-09-23 Noveon Ip Holdings Corp. Dosage form of N-acetyl cysteine
WO2002094172A2 (en) 2001-05-22 2002-11-28 Euro-Celtique Compartmentalized dosage form
US20030064122A1 (en) 2001-05-23 2003-04-03 Endo Pharmaceuticals, Inc. Abuse resistant pharmaceutical composition containing capsaicin
US7968119B2 (en) * 2001-06-26 2011-06-28 Farrell John J Tamper-proof narcotic delivery system
EP2311460A1 (en) 2001-07-06 2011-04-20 Endo Pharmaceuticals Inc. Oxymorphone controlled release formulations
US8329216B2 (en) 2001-07-06 2012-12-11 Endo Pharmaceuticals Inc. Oxymorphone controlled release formulations
EP1404331B1 (en) 2001-07-06 2007-10-31 Penwest Pharmaceuticals Co. Sustained release formulations of oxymorphone
JP2003020517A (en) 2001-07-10 2003-01-24 Calp Corp Resin composition for compound fiber
JP2003032524A (en) * 2001-07-16 2003-01-31 Olympus Optical Co Ltd Digital camera for microscope
US20030157168A1 (en) 2001-08-06 2003-08-21 Christopher Breder Sequestered antagonist formulations
KR20040060917A (en) 2001-08-06 2004-07-06 유로-셀티크 소시에떼 아노뉨 Compositions and methods to prevent abuse of opioids
US7144587B2 (en) * 2001-08-06 2006-12-05 Euro-Celtique S.A. Pharmaceutical formulation containing opioid agonist, opioid antagonist and bittering agent
BR0212020A (en) 2001-08-06 2005-08-16 Euro Celtique Sa Dosage forms, methods for preventing abuse of a dosage form, methods for preventing diversion of a dosage form, methods for treating pain and method of preparing a dosage form
US20030049272A1 (en) 2001-08-30 2003-03-13 Yatindra Joshi Pharmaceutical composition which produces irritation
US6691698B2 (en) 2001-09-14 2004-02-17 Fmc Technologies Inc. Cooking oven having curved heat exchanger
US20030059467A1 (en) 2001-09-14 2003-03-27 Pawan Seth Pharmaceutical composition comprising doxasozin
US20030059397A1 (en) 2001-09-17 2003-03-27 Lyn Hughes Dosage forms
US20030092724A1 (en) 2001-09-18 2003-05-15 Huaihung Kao Combination sustained release-immediate release oral dosage forms with an opioid analgesic and a non-opioid analgesic
EP1429734B1 (en) 2001-09-21 2007-12-26 Egalet A/S Controlled release solid dispersions of carvedilol
US20040253310A1 (en) 2001-09-21 2004-12-16 Gina Fischer Morphine polymer release system
CA2459976A1 (en) 2001-09-26 2003-04-03 Penwest Pharmaceuticals Company Opioid formulations having reduced potential for abuse
AU2002342755A1 (en) 2001-09-26 2003-04-14 Klaus-Jurgen Steffens Method and device for producing granulates that comprise at least one pharmaceutical active substance
US6837696B2 (en) 2001-09-28 2005-01-04 Mcneil-Ppc, Inc. Apparatus for manufacturing dosage forms
JP2005509605A (en) 2001-09-28 2005-04-14 マクニール−ピーピーシー・インコーポレイテッド A dosage form comprising an edible composition and an edible skin
DE60210317T2 (en) 2001-10-09 2006-12-21 The Procter & Gamble Company, Cincinnati AQUEOUS COMPOSITIONS FOR SURFACE TREATMENT
US6592901B2 (en) 2001-10-15 2003-07-15 Hercules Incorporated Highly compressible ethylcellulose for tableting
JP2003125706A (en) 2001-10-23 2003-05-07 Lion Corp Mouth freshening preparation
US20030104052A1 (en) * 2001-10-25 2003-06-05 Bret Berner Gastric retentive oral dosage form with restricted drug release in the lower gastrointestinal tract
CA2409552A1 (en) 2001-10-25 2003-04-25 Depomed, Inc. Gastric retentive oral dosage form with restricted drug release in the lower gastrointestinal tract
US20030152622A1 (en) 2001-10-25 2003-08-14 Jenny Louie-Helm Formulation of an erodible, gastric retentive oral diuretic
WO2003037244A2 (en) 2001-10-29 2003-05-08 Therics, Inc. System for manufacturing controlled release dosage forms, such as a zero-order release profile dosage form manufactured by three-dimensional printing
US20040126428A1 (en) * 2001-11-02 2004-07-01 Lyn Hughes Pharmaceutical formulation including a resinate and an aversive agent
CA2464528A1 (en) 2001-11-02 2003-05-15 Elan Corporation, Plc Pharmaceutical composition
US20030175345A1 (en) 2001-12-06 2003-09-18 Hite Michael P. Isoflavone composition for oral delivery
FR2833838B1 (en) * 2001-12-21 2005-09-16 Ellipse Pharmaceuticals METHOD FOR MANUFACTURING A TABLET INCLUDING A MORPHINIC ANALGESIC AND TABLET OBTAINED
AUPS044502A0 (en) 2002-02-11 2002-03-07 Commonwealth Scientific And Industrial Research Organisation Novel catalysts and processes for their preparation
US20040033253A1 (en) 2002-02-19 2004-02-19 Ihor Shevchuk Acyl opioid antagonists
US20030158265A1 (en) 2002-02-20 2003-08-21 Ramachandran Radhakrishnan Orally administrable pharmaceutical formulation comprising pseudoephedrine hydrochloride and process for preparing the same
US20030190343A1 (en) 2002-03-05 2003-10-09 Pfizer Inc. Palatable pharmaceutical compositions for companion animals
US6572889B1 (en) 2002-03-07 2003-06-03 Noveon Ip Holdings Corp. Controlled release solid dosage carbamazepine formulations
US6753009B2 (en) * 2002-03-13 2004-06-22 Mcneil-Ppc, Inc. Soft tablet containing high molecular weight polyethylene oxide
US6476203B1 (en) 2002-03-14 2002-11-05 Xinxian Zhao Safe pharmaceutical composition for treating and preventing infertility and increasing immune function
ES2546010T3 (en) 2002-04-05 2015-09-17 Euro-Celtique S.A. Pharmaceutical preparation containing oxycodone and naloxone
DE10217232B4 (en) 2002-04-18 2004-08-19 Ticona Gmbh Process for the production of filled granules from polyethylene of high or ultra-high molecular weight
WO2003089506A1 (en) 2002-04-22 2003-10-30 Purdue Research Foundation Hydrogels having enhanced elasticity and mechanical strength properties
CA2486075A1 (en) 2002-05-13 2003-11-20 Endo Pharmaceuticals Inc. Abuse-resistant opioid solid dosage form
RU2004134728A (en) 2002-05-31 2005-06-10 Алза Корпорейшн (Us) DOSED FORMS AND COMPOSITIONS FOR THE OSMOTIC DELIVERY OF VARIOUS DOSAGE OXYCODONE
DE10250083A1 (en) 2002-06-17 2003-12-24 Gruenenthal Gmbh Dosage form protected against abuse
US7776314B2 (en) 2002-06-17 2010-08-17 Grunenthal Gmbh Abuse-proofed dosage system
US20040011806A1 (en) 2002-07-17 2004-01-22 Luciano Packaging Technologies, Inc. Tablet filler device with star wheel
US20070196481A1 (en) 2002-07-25 2007-08-23 Amidon Gregory E Sustained-release tablet composition
CA2496110A1 (en) 2002-08-21 2004-03-04 Phoqus Pharmaceuticals Limited Use of an aqueous solution of citric acid and a water-soluble sugar like lactitol as granulation liquid in the manufacture of tablets
US7388068B2 (en) 2002-08-21 2008-06-17 Clariant Produkte (Deutschland) Gmbh Copolymers made of alkylene oxides and glycidyl ethers and use thereof as polymerizable emulsifiers
RU2326654C2 (en) 2002-09-17 2008-06-20 Уайт Oral compositions
PL215110B1 (en) 2002-09-20 2013-10-31 Fmc Corp Cosmetic composition containing microcrystalline cellulose
WO2004026308A1 (en) 2002-09-21 2004-04-01 Shuyi Zhang Sustained release compound of acetamidophenol and tramadol
JP5189242B2 (en) 2002-09-23 2013-04-24 アルケルメス ファーマ アイルランド リミテッド Abuse-resistant pharmaceutical composition
JP2004143071A (en) 2002-10-23 2004-05-20 Hosokawa Funtai Gijutsu Kenkyusho:Kk Method for producing medicine-containing composite particle and medicine-containing composite particle
JP2006507277A (en) 2002-10-25 2006-03-02 ラボファーマ インコーポレイテッド 24 hour sustained release tramadol formulation
DE10250084A1 (en) 2002-10-25 2004-05-06 Grünenthal GmbH Dosage form protected against abuse
DE10250088A1 (en) * 2002-10-25 2004-05-06 Grünenthal GmbH Dosage form protected against abuse
US20050191244A1 (en) 2002-10-25 2005-09-01 Gruenenthal Gmbh Abuse-resistant pharmaceutical dosage form
DE10250087A1 (en) 2002-10-25 2004-05-06 Grünenthal GmbH Dosage form protected against abuse
DE10252667A1 (en) * 2002-11-11 2004-05-27 Grünenthal GmbH New spiro-((cyclohexane)-tetrahydropyrano-(3,4-b)-indole) derivatives, are ORL1 receptor ligands useful e.g. for treating anxiety, depression, epilepsy, senile dementia, withdrawal symptoms or especially pain
US7018658B2 (en) 2002-11-14 2006-03-28 Synthon Bv Pharmaceutical pellets comprising tamsulosin
US20040121003A1 (en) 2002-12-19 2004-06-24 Acusphere, Inc. Methods for making pharmaceutical formulations comprising deagglomerated microparticles
US20040185097A1 (en) 2003-01-31 2004-09-23 Glenmark Pharmaceuticals Ltd. Controlled release modifying complex and pharmaceutical compositions thereof
US7442387B2 (en) 2003-03-06 2008-10-28 Astellas Pharma Inc. Pharmaceutical composition for controlled release of active substances and manufacturing method thereof
ATE454169T1 (en) 2003-03-13 2010-01-15 Controlled Chemicals Inc OXYCODONE CONJUGATES WITH LOWER ABUSE POTENTIAL AND EXTENDED DURATION
ES2360102T3 (en) 2003-03-26 2011-05-31 Egalet A/S SYSTEM FOR CONTROLLED RELEASE OF MORPHINE.
DE602004025159D1 (en) 2003-03-26 2010-03-04 Egalet As Matrix preparations for the controlled administration of drugs
MY135852A (en) 2003-04-21 2008-07-31 Euro Celtique Sa Pharmaceutical products
US9579286B2 (en) * 2003-04-21 2017-02-28 Purdue Pharma L.P. Tamper resistant dosage form comprising co-extruded, sequestered adverse agent particles and process of making same
EP2316440A1 (en) 2003-04-30 2011-05-04 Purdue Pharma L.P. Transdermal dosage form comprising an active agent component and an adverse agent component at the distal site of the active agent layer and one fluid communication between the surface of the active agent and the adverse agent
US8906413B2 (en) 2003-05-12 2014-12-09 Supernus Pharmaceuticals, Inc. Drug formulations having reduced abuse potential
HU227142B1 (en) * 2003-07-02 2010-08-30 Egis Gyogyszergyar Nyilvanosan Capsule of improved release containing fluconazole
US6886808B2 (en) * 2003-07-14 2005-05-03 Magic Plastics, Inc. Axially actuated drain valve for pools and spas
US20050015730A1 (en) 2003-07-14 2005-01-20 Srimanth Gunturi Systems, methods and computer program products for identifying tab order sequence of graphically represented elements
DE102004020220A1 (en) 2004-04-22 2005-11-10 Grünenthal GmbH Process for the preparation of a secured against misuse, solid dosage form
RU2339365C2 (en) 2003-08-06 2008-11-27 Грюненталь Гмбх Drug dosage form, protected from unintended application
US8075872B2 (en) * 2003-08-06 2011-12-13 Gruenenthal Gmbh Abuse-proofed dosage form
DE102005005446A1 (en) 2005-02-04 2006-08-10 Grünenthal GmbH Break-resistant dosage forms with sustained release
DE10361596A1 (en) 2003-12-24 2005-09-29 Grünenthal GmbH Process for producing an anti-abuse dosage form
DE502004004205D1 (en) 2003-08-06 2007-08-09 Gruenenthal Gmbh AGAINST MISUSE SECURED PHARMACEUTICAL FORM
US20050063214A1 (en) 2003-09-22 2005-03-24 Daisaburo Takashima Semiconductor integrated circuit device
US20060194826A1 (en) 2003-09-25 2006-08-31 Euro-Celtique S.A. Pharmaceutical combinations of hydrocodone and naltrexone
BRPI0414941A (en) 2003-09-30 2006-11-07 Alza Corp osmotically driven active agent dispensing device providing an upward release profile
US20060172006A1 (en) 2003-10-10 2006-08-03 Vincent Lenaerts Sustained-release tramadol formulations with 24-hour clinical efficacy
US20060009478A1 (en) 2003-10-15 2006-01-12 Nadav Friedmann Methods for the treatment of back pain
RU2006118323A (en) 2003-10-29 2007-12-10 Алза Корпорейшн (Us) MEDICINAL FORMS OF OXYCODON WITH CONTROLLED RELEASE FOR ONE-TIME ORAL DOSAGE
EP1689368B1 (en) 2003-12-04 2016-09-28 Bend Research, Inc Spray-congeal process using an extruder for preparing multiparticulate crystalline drug compositions
EP1691892B1 (en) 2003-12-09 2007-02-28 Euro-Celtique S.A. Tamper resistant co-extruded dosage form containing an active agent and an adverse agent and process of making same
WO2005060942A1 (en) 2003-12-19 2005-07-07 Aurobindo Pharma Ltd Extended release pharmaceutical composition of metformin
DE10360792A1 (en) 2003-12-23 2005-07-28 Grünenthal GmbH Spirocyclic cyclohexane derivatives
EP1701706A2 (en) 2003-12-29 2006-09-20 Alza Corporation Novel drug compositions and dosage forms
US20070196396A1 (en) 2004-02-11 2007-08-23 Rubicon Research Private Limited Controlled release pharmaceutical compositions with improved bioavailability
TWI350762B (en) 2004-02-12 2011-10-21 Euro Celtique Sa Particulates
GB0403098D0 (en) 2004-02-12 2004-03-17 Euro Celtique Sa Extrusion
GB0403100D0 (en) 2004-02-12 2004-03-17 Euro Celtique Sa Particulates
DK2074989T3 (en) 2004-02-23 2014-02-03 Euro Celtique Sa ABUSE SAFETY TRANSDERMAL OPIOID DELIVERY DEVICE
US20050220877A1 (en) 2004-03-31 2005-10-06 Patel Ashish A Bilayer tablet comprising an antihistamine and a decongestant
PL1740156T3 (en) 2004-04-22 2011-12-30 Gruenenthal Gmbh Method for the production of an abuse-proof, solid form of administration
WO2005105036A1 (en) 2004-04-28 2005-11-10 Natco Pharma Limited Controlled release mucoadhesive matrix formulation containing tolterodine and a process for its preparation
US20050271594A1 (en) 2004-06-04 2005-12-08 Groenewoud Pieter J Abuse resistent pharmaceutical composition
TWI356036B (en) 2004-06-09 2012-01-11 Smithkline Beecham Corp Apparatus and method for pharmaceutical production
DK1612203T3 (en) 2004-06-28 2007-12-03 Gruenenthal Gmbh Crystalline forms of (-) - (1R, 2R) -3- (3-dimethylamino-1-ethyl-2-methylpropyl) phenol hydrochloride
ITMI20041317A1 (en) 2004-06-30 2004-09-30 Ibsa Inst Biochimique Sa PHARMACEUTICAL FORMULATIONS FOR THE SAFE ADMINISTRATION OF DRUGS USED IN THE TREATMENT OF DRUG ADDICTION AND PROCEDURE FOR THEIR OBTAINING
PL1765303T5 (en) 2004-07-01 2023-05-22 Grünenthal GmbH Oral dosage form safeguarded against abuse
JP5700904B2 (en) 2004-07-01 2015-04-15 グリューネンタール・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング Abuse prevention oral dosage form containing (1R, 2R) -3- (3-dimethylamino-1-ethyl-2-methyl-propyl) phenol
DE102004032049A1 (en) 2004-07-01 2006-01-19 Grünenthal GmbH Anti-abuse, oral dosage form
AR049839A1 (en) 2004-07-01 2006-09-06 Gruenenthal Gmbh PROCEDURE FOR THE PRODUCTION OF A SOLID PHARMACEUTICAL FORM, PROTECTED AGAINST ABUSE
EP1771152B1 (en) 2004-07-27 2008-05-28 Unilever Plc Hair care compositions
GB2418854B (en) * 2004-08-31 2009-12-23 Euro Celtique Sa Multiparticulates
US20060068009A1 (en) 2004-09-30 2006-03-30 Scolr Pharma, Inc. Modified release ibuprofen dosage form
US20070077297A1 (en) 2004-09-30 2007-04-05 Scolr Pharma, Inc. Modified release ibuprofen dosage form
US7426948B2 (en) 2004-10-08 2008-09-23 Phibrowood, Llc Milled submicron organic biocides with narrow particle size distribution, and uses thereof
US20070231268A1 (en) 2004-11-24 2007-10-04 Acura Pharmaceuticals, Inc. Methods and compositions for deterring abuse of orally administered pharmaceutical products
US20060177380A1 (en) 2004-11-24 2006-08-10 Acura Pharmaceuticals, Inc. Methods and compositions for deterring abuse of orally administered pharmaceutical products
US20080152595A1 (en) 2004-11-24 2008-06-26 Acura Pharmaceuticals, Inc. Methods and compositions for deterring abuse of orally administered pharmaceutical products
JP5576591B2 (en) 2005-01-26 2014-08-20 大鵬薬品工業株式会社 Anticancer agent containing α, α, α-trifluorothymidine and thymidine phosphorylase inhibitor
CA2594373A1 (en) 2005-01-28 2006-08-03 Euro-Celtique S.A. Alcohol resistant dosage forms
DE102005005449A1 (en) 2005-02-04 2006-08-10 Grünenthal GmbH Process for producing an anti-abuse dosage form
FR2889810A1 (en) 2005-05-24 2007-02-23 Flamel Technologies Sa ORAL MEDICINAL FORM, MICROPARTICULAR, ANTI-MEASUREMENT
RU2007133601A (en) 2005-02-10 2009-03-20 Лайфсайкл Фарма А/С (Dk) SUSTAINABLE PHARMACEUTICAL COMPOSITION CONTAINING A FIXED DOSE OF A COMBINATION OF Phenofibrate and an HMG-CoA reductase inhibitor
US20060194759A1 (en) 2005-02-25 2006-08-31 Eidelson Stewart G Topical compositions and methods for treating pain and inflammation
EP1695700A1 (en) 2005-02-28 2006-08-30 Euro-Celtique S.A. Dosage form containing oxycodone and naloxone
US20060204575A1 (en) 2005-03-11 2006-09-14 Hengsheng Feng Amphetamine formulations
US7732427B2 (en) 2005-03-31 2010-06-08 University Of Delaware Multifunctional and biologically active matrices from multicomponent polymeric solutions
JP5256425B2 (en) 2005-04-08 2013-08-07 リングアル コンセグナ ピーティーワイ エルティーディー Oral delivery system
EP1881819A1 (en) 2005-05-10 2008-01-30 Novartis AG Extrusion process for making compositions with poorly compressible therapeutic compounds
CA2611081C (en) 2005-06-03 2016-05-31 Egalet A/S A drug delivery system for delivering active substances dispersed in a dispersion medium
WO2006133733A1 (en) 2005-06-13 2006-12-21 Flamel Technologies Oral dosage form comprising an antimisuse system
WO2007005716A2 (en) 2005-06-30 2007-01-11 Cinergen, Llc Methods of treatment and compositions for use thereof
DE102005032806A1 (en) 2005-07-12 2007-01-18 Röhm Gmbh Use of a partially neutralized, anionic (meth) acrylate copolymer as a coating for the preparation of a dosage form with a release of active ingredient at reduced pH values
US8858993B2 (en) 2005-07-25 2014-10-14 Metrics, Inc. Coated tablet with zero-order or near zero-order release kinetics
US20090155357A1 (en) * 2005-08-01 2009-06-18 Alpharma Inc. Alcohol Resistant Pharmaceutical Formulations
WO2007019058A1 (en) 2005-08-03 2007-02-15 Eastman Chemical Company Tocopheryl polyethylene glycol succinate powder and process for preparing same
US20070048373A1 (en) 2005-08-30 2007-03-01 Cima Labs Inc. Dried milled granulate and methods
WO2007043710A1 (en) 2005-10-14 2007-04-19 The Kitasato Institute Novel dihydropseudoerythromycin derivatives
PL116330U1 (en) 2005-10-31 2007-04-02 Alza Corp Method for the reduction of alcohol provoked rapid increase in the released dose of the orally administered opioide with prolonged liberation
US8329744B2 (en) 2005-11-02 2012-12-11 Relmada Therapeutics, Inc. Methods of preventing the serotonin syndrome and compositions for use thereof
WO2008134071A1 (en) 2007-04-26 2008-11-06 Theraquest Biosciences, Inc. Multimodal abuse resistant extended release formulations
FR2892937B1 (en) 2005-11-10 2013-04-05 Flamel Tech Sa MICROPARTICULAR ORAL PHARMACEUTICAL FORM ANTI-MEASURING
DE102005058569B4 (en) 2005-12-08 2010-07-15 Lts Lohmann Therapie-Systeme Ag Foam wafer with polyvinyl alcohol-polyethylene glycol graft copolymer
US20100172989A1 (en) 2006-01-21 2010-07-08 Abbott Laboratories Abuse resistant melt extruded formulation having reduced alcohol interaction
US20090317355A1 (en) 2006-01-21 2009-12-24 Abbott Gmbh & Co. Kg, Abuse resistant melt extruded formulation having reduced alcohol interaction
US20090022798A1 (en) 2007-07-20 2009-01-22 Abbott Gmbh & Co. Kg Formulations of nonopioid and confined opioid analgesics
JP2009523833A (en) 2006-01-21 2009-06-25 アボット ゲーエムベーハー ウント カンパニー カーゲー Formulations and methods for drug delivery
EP1813276A1 (en) 2006-01-27 2007-08-01 Euro-Celtique S.A. Tamper resistant dosage forms
FR2897267A1 (en) 2006-02-16 2007-08-17 Flamel Technologies Sa MULTIMICROPARTICULAR PHARMACEUTICAL FORMS FOR PER OS ADMINISTRATION
ZA200807571B (en) 2006-03-01 2009-08-26 Ethypharm Sa Crush-resistant tablets intended to prevent accidental misuse and unlawful diversion
MX2008010921A (en) 2006-03-02 2008-09-03 Mallinckrodt Inc Processes for preparing morphinan-6-one products with low levels of alpha, beta-unsaturated ketone compounds.
WO2007103286A2 (en) 2006-03-02 2007-09-13 Spherics, Inc. Rate-controlled bioadhesive oral dosage formulations
US8465759B2 (en) 2006-03-24 2013-06-18 Auxilium Us Holdings, Llc Process for the preparation of a hot-melt extruded laminate
US8173152B2 (en) 2006-03-24 2012-05-08 Auxilium Us Holdings, Llc Stabilized compositions containing alkaline labile drugs
US20070224637A1 (en) 2006-03-24 2007-09-27 Mcauliffe Joseph C Oxidative protection of lipid layer biosensors
US10960077B2 (en) 2006-05-12 2021-03-30 Intellipharmaceutics Corp. Abuse and alcohol resistant drug composition
US9023400B2 (en) 2006-05-24 2015-05-05 Flamel Technologies Prolonged-release multimicroparticulate oral pharmaceutical form
WO2007138466A2 (en) * 2006-06-01 2007-12-06 Wockhardt Ltd Pharmaceutical compositions comprising meloxicam and tramadol combination
US20070292508A1 (en) 2006-06-05 2007-12-20 Balchem Corporation Orally disintegrating dosage forms
US20080069891A1 (en) 2006-09-15 2008-03-20 Cima Labs, Inc. Abuse resistant drug formulation
PL2526932T3 (en) * 2006-06-19 2017-12-29 Alpharma Pharmaceuticals Llc Pharmaceutical composition
CN101091721A (en) 2006-06-22 2007-12-26 孙明 Method for preparing new type asshide
EP2043613A1 (en) 2006-07-14 2009-04-08 Fmc Corporation Solid form
JP4029109B1 (en) 2006-07-18 2008-01-09 タマ生化学株式会社 Complex powder of vitamin E and proline and method for producing the same
SA07280459B1 (en) 2006-08-25 2011-07-20 بيورديو فارما إل. بي. Tamper Resistant Oral Pharmaceutical Dosage Forms Comprising an Opioid Analgesic
US8445018B2 (en) 2006-09-15 2013-05-21 Cima Labs Inc. Abuse resistant drug formulation
US8187636B2 (en) 2006-09-25 2012-05-29 Atlantic Pharmaceuticals, Inc. Dosage forms for tamper prone therapeutic agents
KR101400824B1 (en) 2006-09-25 2014-05-29 후지필름 가부시키가이샤 Resist composition, resin for use in the resist composition, compound for use in the synthesis of the resin, and pattern-forming method usign the resist composition
US20080085304A1 (en) 2006-10-10 2008-04-10 Penwest Pharmaceuticals Co. Robust sustained release formulations
CN101578096A (en) * 2006-10-10 2009-11-11 潘威斯脱药物公司 Robust sustained release formulations
GB0624880D0 (en) 2006-12-14 2007-01-24 Johnson Matthey Plc Improved method for making analgesics
CA2673511A1 (en) 2006-12-22 2008-07-03 Combinatorx, Incorporated Pharmaceutical compositions for treatment of parkinson's disease and related disorders
DE102006062120A1 (en) 2006-12-22 2008-06-26 Grünenthal GmbH Pharmaceutical composition for acne treatment
NZ577560A (en) 2007-01-16 2012-01-12 Egalet Ltd Use of i) a polyglycol and ii) an active drug substance for the preparation of a pharmaceutical composition for i) mitigating the risk of alcohol induced dose dumping and/or ii) reducing the risk of drug abuse
WO2008094877A2 (en) 2007-01-30 2008-08-07 Drugtech Corporation Compositions for oral delivery of pharmaceuticals
CN100579525C (en) 2007-02-02 2010-01-13 东南大学 Sustained release preparation of licardipine hydrochloride and its preparing process
EP2109465B1 (en) 2007-02-08 2012-04-11 Kempharm, Inc. Polar hydrophilic prodrugs of amphetamine and other stimulants and processes for making and using the same
CN101057849A (en) 2007-02-27 2007-10-24 齐齐哈尔医学院 Slow-releasing preparation containing metformin hydrochloride and glipizide and its preparation method
EP2144599B1 (en) 2007-03-02 2010-08-04 Farnam Companies, Inc. Sustained release pellets comprising wax-like material
EP1980245A1 (en) 2007-04-11 2008-10-15 Cephalon France Bilayer lyophilized pharmaceutical compositions and methods of making and using same
US20080260836A1 (en) 2007-04-18 2008-10-23 Thomas James Boyd Films Comprising a Plurality of Polymers
EP2586428B1 (en) 2007-04-26 2023-11-08 Sublimity Therapeutics Limited Manufacture of multiple minicapsules
US20110020408A1 (en) 2007-05-17 2011-01-27 Ranbaxy Laboratories Limited multilayered modified release formulation comprising amoxicillin and clavulanate
US8202542B1 (en) 2007-05-31 2012-06-19 Tris Pharma Abuse resistant opioid drug-ion exchange resin complexes having hybrid coatings
AU2008258596B2 (en) 2007-06-04 2013-02-14 Egalet Ltd Controlled release pharmaceutical compositions for prolonged effect
US20100035886A1 (en) 2007-06-21 2010-02-11 Veroscience, Llc Parenteral formulations of dopamine agonists
EP2170051A1 (en) 2007-07-01 2010-04-07 Joseph Peter Habboushe Combination tablet with chewable outer layer
CA2690829A1 (en) 2007-07-20 2009-01-29 Abbott Gmbh & Co. Kg Formulations of nonopioid and confined opioid analgesics
EP2200591A2 (en) 2007-09-11 2010-06-30 Ranbaxy Laboratories Limited Controlled release pharmaceutical dosage forms of trimetazidine
JP5730572B2 (en) 2007-09-13 2015-06-10 シマ ラブス インク． Abuse resistant formulation
WO2009051819A1 (en) 2007-10-17 2009-04-23 Axxia Pharmaceuticals, Llc Polymeric drug delivery systems and thermoplastic extrusion processes for producing such systems
CA2706596A1 (en) 2007-11-23 2009-05-28 Protect Pharmaceutical Corporation Tapentadol compositions
CA2706658A1 (en) 2007-12-06 2009-06-18 Durect Corporation Methods useful for the treatment of pain, arthritic conditions or inflammation associated with a chronic condition
ES2388470T3 (en) 2007-12-12 2012-10-15 Basf Se Salts of active ingredients with polymeric counterions
JP5651818B2 (en) 2007-12-17 2015-01-14 パラディン ラブス インコーポレーテッド Controlled release formulation to prevent misuse
EP2249811A1 (en) 2008-01-25 2010-11-17 Grünenthal GmbH Pharmaceutical dosage form
KR100970665B1 (en) 2008-02-04 2010-07-15 삼일제약주식회사 Sustained release tablet containing alfuzosin or its salt
EA201071035A1 (en) 2008-03-05 2011-04-29 Панацеа Биотек Лимитед PHARMACEUTICAL COMPOSITIONS OF MODIFIED SHIPPING, CONTAINING MYCOPHENOLATE, AND METHOD OF THEIR RECEIVING
US8372432B2 (en) 2008-03-11 2013-02-12 Depomed, Inc. Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic
TWI519322B (en) 2008-04-15 2016-02-01 愛戴爾製藥股份有限公司 Compositions comprising weakly basic drugs and controlled-release dosage forms
JP2011526928A (en) 2008-07-03 2011-10-20 ノバルティス アーゲー Melt granulation method
WO2010022193A2 (en) 2008-08-20 2010-02-25 Board Of Regents, The University Of Texas System Hot-melt extrusion of modified release multi-particulates
FR2936709B1 (en) 2008-10-02 2012-05-11 Ethypharm Sa ALCOHOL-RESISTANT TABLETS.
WO2010044842A1 (en) 2008-10-16 2010-04-22 University Of Tennessee Research Foundation Tamper resistant oral dosage forms containing an embolizing agent
MY161550A (en) 2008-10-27 2017-04-28 Alza Corp Extended release oral acetaminophen/tramadol dosage form
US20100260844A1 (en) * 2008-11-03 2010-10-14 Scicinski Jan J Oral pharmaceutical dosage forms
EP2376065A2 (en) 2008-11-14 2011-10-19 Portola Pharmaceuticals, Inc. Solid composition for controlled release of ionizable active agents with poor aqueous solubility at low ph and methods of use thereof
PL2379111T3 (en) 2008-12-12 2013-08-30 Paladin Labs Inc Narcotic drug formulations with decreased abuse potential
US8486449B2 (en) 2008-12-16 2013-07-16 Paladin Labs Inc. Misuse preventative, controlled release formulation
EP2389169A1 (en) 2009-01-26 2011-11-30 Egalet A/S Controlled release formulations with continuous efficacy
EP2393487B1 (en) 2009-02-06 2016-11-02 Egalet Ltd. Pharmaceutical compositions resistant to abuse
SI2408436T1 (en) 2009-03-18 2017-06-30 Evonik Roehm Gmbh Controlled release pharmaceutical composition with resistance against the influence of ethanol employing a coating comprising neutral vinyl polymers and excipients
EP2246063A1 (en) 2009-04-29 2010-11-03 Ipsen Pharma S.A.S. Sustained release formulations comprising GnRH analogues
WO2010141505A1 (en) 2009-06-01 2010-12-09 Protect Pharmaceutical Corporation Abuse-resistant delivery systems
GB0909680D0 (en) 2009-06-05 2009-07-22 Euro Celtique Sa Dosage form
EP2445487A2 (en) * 2009-06-24 2012-05-02 Egalet Ltd. Controlled release formulations
WO2011008298A2 (en) 2009-07-16 2011-01-20 Nectid, Inc. Novel axomadol dosage forms
AU2010300641B2 (en) 2009-09-30 2016-03-17 Acura Pharmaceuticals, Inc. Methods and compositions for deterring abuse
JP5529884B2 (en) 2009-11-13 2014-06-25 森六ケミカルズ株式会社 Method for producing fine powder and fine powder produced by the same method
WO2011068722A1 (en) 2009-12-01 2011-06-09 Noven Pharmaceuticals, Inc. Transdermal testosterone device and delivery
EP2531176B1 (en) 2010-02-03 2016-09-07 Grünenthal GmbH Preparation of a powdery pharmaceutical composition by means of an extruder
US9306723B2 (en) * 2010-02-20 2016-04-05 Google Technology Holdings LLC Multi-carrier control signaling in wireless communication system
GB201003731D0 (en) 2010-03-05 2010-04-21 Univ Strathclyde Immediate/delayed drug delivery
JP5819329B2 (en) 2010-03-09 2015-11-24 アルカーメス ファーマ アイルランド リミテッド Alcohol-resistant enteric pharmaceutical composition
ES2592277T3 (en) 2010-04-02 2016-11-29 Buzzz Pharmaceuticals Limited Transdermal deterrent formulations of abuse of opioid agonists and agonists
CA2832436C (en) 2010-04-07 2018-08-14 Lupin Limited Controlled release pharmaceutical compositions of tapentadol
GB201006200D0 (en) 2010-04-14 2010-06-02 Ayanda As Composition
ES2689520T3 (en) 2010-04-23 2018-11-14 Kempharm, Inc. Therapeutic formulation to reduce drug side effects
FR2959935B1 (en) 2010-05-14 2013-02-08 Ethypharm Sa ALCOHOL-RESISTANT ORAL PHARMACEUTICAL FORM
FR2960775A1 (en) 2010-06-07 2011-12-09 Ethypharm Sa MICROGRANULES RESISTANT TO MISMATCH
AR082861A1 (en) * 2010-09-02 2013-01-16 Gruenenthal Gmbh ALTERATION RESISTANT DOSAGE FORM INCLUDING AN ANIONIC POLYMER
NZ607392A (en) 2010-09-02 2015-03-27 Gruenenthal Chemie Tamper resistant dosage form comprising inorganic salt
PE20131126A1 (en) 2010-09-02 2013-10-21 Gruenenthal Chemie ALTERATION RESISTANT DOSAGE FORM INCLUDING AN ANIONIC POLYMER
WO2012061779A1 (en) 2010-11-04 2012-05-10 Abbott Gmbh & Co. Kg Drug formulations
US20120231083A1 (en) 2010-11-18 2012-09-13 The Board Of Trustees Of The University Of Illinois Sustained release cannabinoid medicaments
GB201020895D0 (en) 2010-12-09 2011-01-26 Euro Celtique Sa Dosage form
CA2822769C (en) 2010-12-23 2016-10-04 Purdue Pharma L.P. Tamper resistant solid oral dosage forms
AU2012219322A1 (en) 2011-02-17 2013-05-09 QRxPharma Ltd. Technology for preventing abuse of solid dosage forms
MX351584B (en) 2011-03-04 2017-10-20 Gruenenthal Gmbh Aqueous pharmaceutical formulation of tapentadol for oral administration.
EP3272343B1 (en) 2011-04-29 2020-02-12 Grünenthal GmbH Tapentadol for preventing and treating depression and anxiety
US8858963B1 (en) 2011-05-17 2014-10-14 Mallinckrodt Llc Tamper resistant composition comprising hydrocodone and acetaminophen for rapid onset and extended duration of analgesia
EP2714015B1 (en) 2011-06-01 2017-03-15 FMC Corporation Controlled release solid dose forms
WO2013003845A1 (en) 2011-06-30 2013-01-03 Neos Therapeutics, Lp Abuse resistant drug forms
EP2736495B1 (en) 2011-07-29 2017-08-23 Grünenthal GmbH Tamper-resistant tablet providing immediate drug release
DK2736497T3 (en) 2011-07-29 2017-11-13 Gruenenthal Gmbh Shock-resistant tablet that provides an immediate release of a drug.
WO2013025449A1 (en) 2011-08-16 2013-02-21 Merck Sharp & Dohme Corp. Use of inorganic matrix and organic polymer combinations for preparing stable amorphous dispersions
FR2979242A1 (en) 2011-08-29 2013-03-01 Sanofi Sa COMPRESSES AGAINST ABUSIVE USE, BASED ON PARACETAMOL AND OXYCODONE
AR088250A1 (en) 2011-10-06 2014-05-21 Gruenenthal Gmbh ORAL PHARMACEUTICAL DOSAGE FORM RESISTANT TO ALTERATION UNDERSTANDING OPIOID AGONIST AND OPIOID ANTAGONIST
WO2013072395A1 (en) 2011-11-17 2013-05-23 Grünenthal GmbH Tamper-resistant oral pharmaceutical dosage form comprising a pharmacologically active ingredient, an opioid antagonist and/or aversive agent, polyalkylene oxide and anionic polymer
US20150265536A1 (en) 2011-12-09 2015-09-24 Purdue Pharma L.P. Pharmaceutical dosage forms comprising poly(epsilon-caprolactone) and polyethylene oxide
EP2606879A1 (en) 2011-12-21 2013-06-26 Hexal AG Multiple unit pellet tablet formulation comprising an opioid
JP2013155124A (en) 2012-01-30 2013-08-15 Moriroku Chemicals Co Ltd Bulk powder of medicine and method of producing the same
WO2013127830A1 (en) 2012-02-28 2013-09-06 Grünenthal GmbH Tamper-resistant pharmaceutical dosage form comprising nonionic surfactant
MX356421B (en) 2012-02-28 2018-05-29 Gruenenthal Gmbh Tamper-resistant dosage form comprising pharmacologically active compound and anionic polymer.
NZ629468A (en) 2012-03-02 2017-08-25 Rhodes Pharmaceuticals Lp Tamper resistant immediate release formulations
LT2838512T (en) * 2012-04-18 2018-11-12 GrĆ¼nenthal GmbH Tamper resistant and dose-dumping resistant pharmaceutical dosage form
EP2838536B1 (en) 2012-04-18 2017-08-09 Mallinckrodt LLC Immediate release pharmaceutical compositions with abuse deterrent properties
US10064945B2 (en) 2012-05-11 2018-09-04 Gruenenthal Gmbh Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc
EA029171B1 (en) 2012-05-11 2018-02-28 Грюненталь Гмбх Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc and process for manufacture thereof
EP2880011A4 (en) 2012-08-01 2016-03-23 Acura Pharmaceuticals Inc Stabilization of one-pot methamphetamine synthesis systems
HUE031603T2 (en) 2012-08-27 2017-07-28 Evonik Roehm Gmbh Pharmaceutical or nutraceutical composition with sustained release characteristic and with resistance against the influence of ethanol
US10639283B2 (en) 2012-08-27 2020-05-05 Evonik Operations Gmbh Gastric resistant pharmaceutical or nutraceutical composition with resistance against the influence of ethanol
WO2014038593A2 (en) 2012-09-05 2014-03-13 テイカ製薬株式会社 Granulated material for tablet that rapidly disintegrates in mouth
WO2014059512A1 (en) 2012-10-15 2014-04-24 Isa Odidi Oral drug delivery formulations
US10420729B2 (en) * 2013-03-15 2019-09-24 R.P. Scherer Technologies, Llc Abuse resistant capsule
CN105209021A (en) 2013-03-15 2015-12-30 马林克罗特有限公司 Compositions comprising an opioid and an additional active pharmaceutical ingredient for rapid onset and extended duration of analgesia that may be administered without regard to food
US9517208B2 (en) * 2013-03-15 2016-12-13 Purdue Pharma L.P. Abuse-deterrent dosage forms
US10154966B2 (en) * 2013-05-29 2018-12-18 Grünenthal GmbH Tamper-resistant dosage form containing one or more particles
MX2015016254A (en) 2013-05-29 2016-04-20 Gruenenthal Gmbh Tamper resistant dosage form with bimodal release profile.
CA2817728A1 (en) 2013-05-31 2014-11-30 Pharmascience Inc. Abuse deterrent immediate release formulation
KR20160031526A (en) 2013-07-12 2016-03-22 그뤼넨탈 게엠베하 Tamper-resistant dosage form containing ethylene-vinyl acetate polymer
CA3042642A1 (en) 2013-08-12 2015-02-19 Pharmaceutical Manufacturing Research Services, Inc. Extruded immediate release abuse deterrent pill
US9770514B2 (en) 2013-09-03 2017-09-26 ExxPharma Therapeutics LLC Tamper-resistant pharmaceutical dosage forms
WO2015048597A1 (en) 2013-09-30 2015-04-02 Daya Drug Discoveries, Inc. Prevention of illicit methamphetamine manufacture from pseudoephedrine using food flavor excipients
WO2015065547A1 (en) 2013-10-31 2015-05-07 Cima Labs Inc. Immediate release abuse-deterrent granulated dosage forms
WO2015103379A1 (en) 2013-12-31 2015-07-09 Kashiv Pharma, Llc Abuse-resistant drug formulations
WO2015120201A1 (en) * 2014-02-05 2015-08-13 Kashiv Pharma, Llc Abuse-resistant drug formulations with built-in overdose protection
US20160089439A1 (en) 2014-09-28 2016-03-31 Satara Pharmaceuticals, LLC Prevention of Illicit Manufacutre of Methamphetamine from Pseudoephedrine Using Food Flavor Excipients
US20170112766A1 (en) * 2015-04-24 2017-04-27 Grünenthal GmbH Tamper-resistant dosage form with immediate release and resistance against solvent extraction
WO2016170097A1 (en) 2015-04-24 2016-10-27 Grünenthal GmbH Tamper-resistant dosage form with immediate release and resistance against solvent extraction
WO2017042325A1 (en) 2015-09-10 2017-03-16 Grünenthal GmbH Protecting oral overdose with abuse deterrent immediate release formulations
US20170296476A1 (en) * 2016-04-15 2017-10-19 Grünenthal GmbH Modified release abuse deterrent dosage forms

Patent Citations (98)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3806603A (en) * 1969-10-13 1974-04-23 W Gaunt Pharmaceutical carriers of plasticized dried milled particles of hydrated cooked rice endosperm
US4070497A (en) * 1971-03-09 1978-01-24 Ppg Industries, Inc. Process of applying and curing a plurality of coatings
US3865108A (en) * 1971-05-17 1975-02-11 Ortho Pharma Corp Expandable drug delivery device
US3966747A (en) * 1972-10-26 1976-06-29 Bristol-Myers Company 9-Hydroxy-6,7-benzomorphans
US4002173A (en) * 1974-07-23 1977-01-11 International Paper Company Diester crosslinked polyglucan hydrogels and reticulated sponges thereof
US4070494A (en) * 1975-07-09 1978-01-24 Bayer Aktiengesellschaft Enteral pharmaceutical compositions
US4262017A (en) * 1978-05-22 1981-04-14 Basf Aktiengesellschaft Preparation of a vitamin E dry powder
US4200704A (en) * 1978-09-28 1980-04-29 Union Carbide Corporation Controlled degradation of poly(ethylene oxide)
US4427681A (en) * 1982-09-16 1984-01-24 Richardson-Vicks, Inc. Thixotropic compositions easily convertible to pourable liquids
US5082668A (en) * 1983-05-11 1992-01-21 Alza Corporation Controlled-release system with constant pushing source
US4744976A (en) * 1984-07-23 1988-05-17 Zetachron, Inc. Erodible matrix for sustained release bioactive composition
US4806337A (en) * 1984-07-23 1989-02-21 Zetachron, Inc. Erodible matrix for sustained release bioactive composition
US4992279A (en) * 1985-07-03 1991-02-12 Kraft General Foods, Inc. Sweetness inhibitor
US5198226A (en) * 1986-01-30 1993-03-30 Syntex (U.S.A.) Inc. Long acting nicardipine hydrochloride formulation
US4667013A (en) * 1986-05-02 1987-05-19 Union Carbide Corporation Process for alkylene oxide polymerization
US4892889A (en) * 1986-11-18 1990-01-09 Basf Corporation Process for making a spray-dried, directly-compressible vitamin powder comprising unhydrolyzed gelatin
US4992278A (en) * 1987-01-14 1991-02-12 Ciba-Geigy Corporation Therapeutic system for sparingly soluble active ingredients
US4892778A (en) * 1987-05-27 1990-01-09 Alza Corporation Juxtaposed laminated arrangement
US5004601A (en) * 1988-10-14 1991-04-02 Zetachron, Inc. Low-melting moldable pharmaceutical excipient and dosage forms prepared therewith
US5200197A (en) * 1989-11-16 1993-04-06 Alza Corporation Contraceptive pill
US5211892A (en) * 1990-07-20 1993-05-18 L'oreal Process for the compaction of a powder mixture providing an absorbent or partially friable compact product and the product obtained by this process
US5508042A (en) * 1991-11-27 1996-04-16 Euro-Celtigue, S.A. Controlled release oxycodone compositions
US5378462A (en) * 1992-08-19 1995-01-03 Kali-Chemie Pharma Gmbh Pancreatin micropellets prepared with polyethylene glycol 4000, paraffin and a lower alcohol by extrusion and rounding
US6699503B1 (en) * 1992-09-18 2004-03-02 Yamanuchi Pharmaceutical Co., Ltd. Hydrogel-forming sustained-release preparation
US5620697A (en) * 1992-12-31 1997-04-15 Orion-Yhtyma Oy Method for preparing matrix-type pharmaceutical compositions through ultrasonic means to accomplish melting
US5601842A (en) * 1993-09-03 1997-02-11 Gruenenthal Gmbh Sustained release drug formulation containing a tramadol salt
US5707636A (en) * 1994-08-03 1998-01-13 Saitec S.R.L. Apparatus and method for preparing solid forms with controlled release of the active ingredient
US20040081694A1 (en) * 1994-11-04 2004-04-29 Euro-Celtique, S.A. Melt-extruded orally administrable opioid formulations
US6009690A (en) * 1994-12-23 2000-01-04 Basf Aktiengesellschaft Process and apparatus for the production of divisible tablets
US5741519A (en) * 1995-03-21 1998-04-21 Basf Aktiengesellschaft The production of active substance compositions in the form of a solid solution of the active substance in a polymer matrix, and active substance compositions produced by this process
US6348469B1 (en) * 1995-04-14 2002-02-19 Pharma Pass Llc Solid compositions containing glipizide and polyethylene oxide
US6355656B1 (en) * 1995-12-04 2002-03-12 Celgene Corporation Phenidate drug formulations having diminished abuse potential
US5866164A (en) * 1996-03-12 1999-02-02 Alza Corporation Composition and dosage form comprising opioid antagonist
US6534089B1 (en) * 1996-04-05 2003-03-18 Alza Corporation Uniform drug delivery therapy
US7176251B1 (en) * 1996-11-05 2007-02-13 Novamont S.P.A. Biodegradable polymeric compositions comprising starch and a thermoplastic polymer
US20020051820A1 (en) * 1997-06-06 2002-05-02 Depomed, Inc. Extending the duration of drug release within the stomach during the fed mode
US6340475B2 (en) * 1997-06-06 2002-01-22 Depomed, Inc. Extending the duration of drug release within the stomach during the fed mode
US6547997B1 (en) * 1997-11-28 2003-04-15 Abbot Laboratories Method for producing solvent-free noncrystalline biologically active substances
US6344535B1 (en) * 1997-12-03 2002-02-05 Bayer Aktiengesellschaft Polyether ester amides
US6375957B1 (en) * 1997-12-22 2002-04-23 Euro-Celtique, S.A. Opioid agonist/opioid antagonist/acetaminophen combinations
US6235825B1 (en) * 1998-03-05 2001-05-22 Mitsui Chemicals, Inc. Polylactic acid resin composition and film therefrom
US6238697B1 (en) * 1998-12-21 2001-05-29 Pharmalogix, Inc. Methods and formulations for making bupropion hydrochloride tablets using direct compression
US6375963B1 (en) * 1999-06-16 2002-04-23 Michael A. Repka Bioadhesive hot-melt extruded film for topical and mucosal adhesion applications and drug delivery and process for preparation thereof
US6562375B1 (en) * 1999-08-04 2003-05-13 Yamanouchi Pharmaceuticals, Co., Ltd. Stable pharmaceutical composition for oral use
US20030044464A1 (en) * 1999-08-31 2003-03-06 Iris Ziegler Sustained-release, oral pharamaceutical forms of formulation
US20110097404A1 (en) * 2000-02-08 2011-04-28 Purdue Pharma L.P. Tamper-resistant oral opioid agonist formulations
US20050095291A1 (en) * 2000-02-08 2005-05-05 Benjamin Oshlack Tamper-resistant oral opioid agonist formulations
US20020015730A1 (en) * 2000-03-09 2002-02-07 Torsten Hoffmann Pharmaceutical formulations and method for making
US8114838B2 (en) * 2000-05-23 2012-02-14 Acorda Therapeutics, Inc. Methods for protecting dopaminergic neurons from stress and promoting proliferation and differentiation of oligodendrocyte progenitors by NRG-2
US20020012701A1 (en) * 2000-06-19 2002-01-31 Karl Kolter Process for producing solid oral dosage forms with sustained release of active ingredient
US6733783B2 (en) * 2000-10-30 2004-05-11 Euro-Celtique S.A. Controlled release hydrocodone formulations
US20030008409A1 (en) * 2001-07-03 2003-01-09 Spearman Steven R. Method and apparatus for determining sunlight exposure
US20030069263A1 (en) * 2001-07-18 2003-04-10 Breder Christopher D. Pharmaceutical combinations of oxycodone and naloxone
US20030021546A1 (en) * 2001-07-30 2003-01-30 Tsuguo Sato Optical fiber ferrule assembly and optical module and optical connector using the same
US20030068392A1 (en) * 2001-08-06 2003-04-10 Richard Sackler Pharmaceutical formulation containing opioid agonist, opioid antagonist and irritant
US20030068375A1 (en) * 2001-08-06 2003-04-10 Curtis Wright Pharmaceutical formulation containing gelling agent
US20090081287A1 (en) * 2001-08-06 2009-03-26 Purdue Pharma L.P. Pharmaceutical Composition Containing Gelling Agent
US7214385B2 (en) * 2001-08-06 2007-05-08 Thomas J. Gruber Pharmaceutical formulation containing dye
US20030064099A1 (en) * 2001-08-06 2003-04-03 Benjamin Oshlack Pharmaceutical formulation containing bittering agent
US7157103B2 (en) * 2001-08-06 2007-01-02 Euro-Celtique S.A. Pharmaceutical formulation containing irritant
US20030068370A1 (en) * 2001-08-06 2003-04-10 Richard Sackler Pharmaceutical formulation containing irritant
US20030068371A1 (en) * 2001-08-06 2003-04-10 Benjamin Oshlack Pharmaceutical formulation containing opioid agonist,opioid antagonist and gelling agent
US20030044458A1 (en) * 2001-08-06 2003-03-06 Curtis Wright Oral dosage form comprising a therapeutic agent and an adverse-effect agent
US20120108622A1 (en) * 2001-08-06 2012-05-03 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US20030068276A1 (en) * 2001-09-17 2003-04-10 Lyn Hughes Dosage forms
US20050058706A1 (en) * 2001-10-24 2005-03-17 Grunenthal Gmbh Delayed release pharmaceutical composition containing 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol
US20030091630A1 (en) * 2001-10-25 2003-05-15 Jenny Louie-Helm Formulation of an erodible, gastric retentive oral dosage form using in vitro disintegration test data
US6723340B2 (en) * 2001-10-25 2004-04-20 Depomed, Inc. Optimal polymer mixtures for gastric retentive tablets
US20090017121A1 (en) * 2001-10-25 2009-01-15 Bret Berner Gastric retained gabapentin dosage form
US20050106249A1 (en) * 2002-04-29 2005-05-19 Stephen Hwang Once-a-day, oral, controlled-release, oxycodone dosage forms
US20040010000A1 (en) * 2002-04-29 2004-01-15 Ayer Atul D. Methods and dosage forms for controlled delivery of oxycodone
US20040052731A1 (en) * 2002-07-05 2004-03-18 Collegium Pharmaceuticals, Inc. Abuse-deterrent pharmaceutical compositions of opiods and other drugs
US20040052844A1 (en) * 2002-09-16 2004-03-18 Fang-Hsiung Hsiao Time-controlled, sustained release, pharmaceutical composition containing water-soluble resins
US20100098758A1 (en) * 2002-10-25 2010-04-22 Gruenenthal Gmbh Abuse-Resistant Dosage Form
US20040091528A1 (en) * 2002-11-12 2004-05-13 Yamanouchi Pharma Technologies, Inc. Soluble drug extended release system
US20050031546A1 (en) * 2003-08-06 2005-02-10 Johannes Bartholomaus Abuse-proffed dosage form
US20070048228A1 (en) * 2003-08-06 2007-03-01 Elisabeth Arkenau-Maric Abuse-proofed dosage form
US8114383B2 (en) * 2003-08-06 2012-02-14 Gruenenthal Gmbh Abuse-proofed dosage form
US7201920B2 (en) * 2003-11-26 2007-04-10 Acura Pharmaceuticals, Inc. Methods and compositions for deterring abuse of opioid containing dosage forms
US20050112067A1 (en) * 2003-11-26 2005-05-26 Vijai Kumar Methods and compositions for deterring abuse of opioid containing dosage forms
US7683072B2 (en) * 2004-03-30 2010-03-23 Purdue Pharma L.P. Oxycodone hydrochloride having less than 25 ppm 14-hydroxycodeinone
US7674800B2 (en) * 2004-03-30 2010-03-09 Purdue Pharma L.P. Oxycodone hydrochloride having less than 25 PPM 14-hydroxycodeinone
US7674799B2 (en) * 2004-03-30 2010-03-09 Purdue Pharma L.P. Oxycodone hydrochloride having less than 25 ppm 14-hydroxycodeinone
US20070065365A1 (en) * 2004-04-21 2007-03-22 Gruenenthal Gmbh Abuse-resistant transdermal system
US20060002859A1 (en) * 2004-07-01 2006-01-05 Elisabeth Arkenau Process for production of an abuse-proofed solid dosage form
US20060039864A1 (en) * 2004-07-01 2006-02-23 Johannes Bartholomaus Abuse-proofed oral dosage form
US8114384B2 (en) * 2004-07-01 2012-02-14 Gruenenthal Gmbh Process for the production of an abuse-proofed solid dosage form
US20060064009A1 (en) * 2004-09-21 2006-03-23 Webler William E Vessel imaging devices and methods
US7939543B2 (en) * 2005-03-04 2011-05-10 Purdue Pharma L.P. Method of reducing α, β unsaturated ketones in opioid compositions
US20070020335A1 (en) * 2005-07-07 2007-01-25 Farnam Companies, Inc. Sustained release pharmaceutical compositions for highly water soluble drugs
US20070092573A1 (en) * 2005-10-24 2007-04-26 Laxminarayan Joshi Stabilized extended release pharmaceutical compositions comprising a beta-adrenoreceptor antagonist
US20100092553A1 (en) * 2005-11-10 2010-04-15 Flamel Technologies anti-misuse microparticulate oral pharmaceutical form
US20080069871A1 (en) * 2006-07-21 2008-03-20 Vaughn Jason M Hydrophobic abuse deterrent delivery system
US20090004267A1 (en) * 2007-03-07 2009-01-01 Gruenenthal Gmbh Dosage Form with Impeded Abuse
US20110020454A1 (en) * 2008-03-13 2011-01-27 Rosa Lamarca Casado Novel dosage and formulation
US20110082214A1 (en) * 2008-05-09 2011-04-07 Gruenthal Gmbh Process for the preparation of a solid dosage form, in particular a tablet, for pharmaceutical use and process for the preparation of a precursor for a solid dosage form, in particular a tablet
US20110038930A1 (en) * 2009-07-22 2011-02-17 Grunenthal Gmbh Hot-melt extruded pharmaceutical dosage form
US20110020451A1 (en) * 2009-07-22 2011-01-27 Grunenthal Gmbh Tamper-resistant dosage form for oxidation-sensitive opioids

Cited By (254)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9387173B2 (en) 2001-08-06 2016-07-12 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US10064825B2 (en) 2001-08-06 2018-09-04 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US8999961B2 (en) 2001-08-06 2015-04-07 Purdue Pharma, L.P. Pharmaceutical formulation containing gelling agent
US8871265B2 (en) 2001-08-06 2014-10-28 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US10071057B2 (en) 2001-08-06 2018-09-11 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US9034376B2 (en) 2001-08-06 2015-05-19 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US9040084B2 (en) 2001-08-06 2015-05-26 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US9968559B2 (en) 2001-08-06 2018-05-15 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US9044435B2 (en) 2001-08-06 2015-06-02 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US10076497B2 (en) 2001-08-06 2018-09-18 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US9877924B2 (en) 2001-08-06 2018-01-30 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US9060976B2 (en) 2001-08-06 2015-06-23 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US10130586B2 (en) 2001-08-06 2018-11-20 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US8609683B2 (en) 2001-08-06 2013-12-17 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US10206881B2 (en) 2001-08-06 2019-02-19 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US9872836B2 (en) 2001-08-06 2018-01-23 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US9867784B2 (en) 2001-08-06 2018-01-16 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US8529948B1 (en) 2001-08-06 2013-09-10 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US10500160B2 (en) 2001-08-06 2019-12-10 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US9867783B2 (en) 2001-08-06 2018-01-16 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US8389007B2 (en) 2001-08-06 2013-03-05 Purdue Pharma L.P. Pharmaceutical composition containing gelling agent
US9861582B2 (en) 2001-08-06 2018-01-09 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US10537526B2 (en) 2001-08-06 2020-01-21 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US8337888B2 (en) 2001-08-06 2012-12-25 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US9693961B2 (en) 2001-08-06 2017-07-04 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US10064824B2 (en) 2001-08-06 2018-09-04 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US11135171B2 (en) 2001-08-06 2021-10-05 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US9861583B2 (en) 2001-08-06 2018-01-09 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US9757341B2 (en) 2001-08-06 2017-09-12 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US9308170B2 (en) 2001-08-06 2016-04-12 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US9517207B2 (en) 2001-08-06 2016-12-13 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US9308171B2 (en) 2001-08-06 2016-04-12 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US9387174B2 (en) 2001-08-06 2016-07-12 Purdue Pharma L.P. Pharmaceutical formulation containing gelling agent
US9707179B2 (en) 2001-09-21 2017-07-18 Egalet Ltd. Opioid polymer release system
US8808745B2 (en) 2001-09-21 2014-08-19 Egalet Ltd. Morphine polymer release system
US9694080B2 (en) 2001-09-21 2017-07-04 Egalet Ltd. Polymer release system
US10369109B2 (en) 2002-06-17 2019-08-06 Grünenthal GmbH Abuse-proofed dosage form
US9675610B2 (en) 2002-06-17 2017-06-13 Grünenthal GmbH Abuse-proofed dosage form
US10525053B2 (en) 2002-07-05 2020-01-07 Collegium Pharmaceutical, Inc. Abuse-deterrent pharmaceutical compositions of opioids and other drugs
US9375428B2 (en) 2003-03-26 2016-06-28 Egalet Ltd. Morphine controlled release system
US8877241B2 (en) 2003-03-26 2014-11-04 Egalet Ltd. Morphine controlled release system
US9884029B2 (en) 2003-03-26 2018-02-06 Egalet Ltd. Morphine controlled release system
US8192722B2 (en) 2003-08-06 2012-06-05 Grunenthal Gmbh Abuse-proof dosage form
US8114383B2 (en) 2003-08-06 2012-02-14 Gruenenthal Gmbh Abuse-proofed dosage form
US20080311049A1 (en) * 2003-08-06 2008-12-18 Grunenthal Gmbh Abuse-proof dosage form
US9629807B2 (en) 2003-08-06 2017-04-25 Grünenthal GmbH Abuse-proofed dosage form
US8420056B2 (en) 2003-08-06 2013-04-16 Grunenthal Gmbh Abuse-proofed dosage form
US10130591B2 (en) 2003-08-06 2018-11-20 Grünenthal GmbH Abuse-proofed dosage form
US20060193782A1 (en) * 2003-08-06 2006-08-31 Johannes Bartholomaus Abuse-proofed dosage form
US8075872B2 (en) 2003-08-06 2011-12-13 Gruenenthal Gmbh Abuse-proofed dosage form
US20080247959A1 (en) * 2003-08-06 2008-10-09 Grunenthal Gmbh Form of administration secured against misuse
US20070183980A1 (en) * 2003-08-06 2007-08-09 Elisabeth Arkenau-Maric Dosage form that is safeguarded from abuse
US20050031546A1 (en) * 2003-08-06 2005-02-10 Johannes Bartholomaus Abuse-proffed dosage form
US10058548B2 (en) 2003-08-06 2018-08-28 Grünenthal GmbH Abuse-proofed dosage form
US8309060B2 (en) 2003-08-06 2012-11-13 Grunenthal Gmbh Abuse-proofed dosage form
US20070003616A1 (en) * 2003-12-24 2007-01-04 Elisabeth Arkenau-Maric Process for the production of an abuse-proofed dosage form
US20090005408A1 (en) * 2003-12-24 2009-01-01 Grunenthal Gmbh Process for the production of an abuse-proofed dosage form
US11224576B2 (en) 2003-12-24 2022-01-18 Grünenthal GmbH Process for the production of an abuse-proofed dosage form
US20080317854A1 (en) * 2004-04-22 2008-12-25 Grunenthal Gmbh Process for the production of an abuse-proofed solid dosage form
US20050236741A1 (en) * 2004-04-22 2005-10-27 Elisabeth Arkenau Process for the production of an abuse-proofed solid dosage form
US10525052B2 (en) 2004-06-12 2020-01-07 Collegium Pharmaceutical, Inc. Abuse-deterrent drug formulations
US20200038330A1 (en) * 2004-07-01 2020-02-06 Grünenthal GmbH Abuse-proofed oral dosage form
US20080248113A1 (en) * 2004-07-01 2008-10-09 Grunenthal Gmbh Abuse-proofed oral dosage form
US20060002859A1 (en) * 2004-07-01 2006-01-05 Elisabeth Arkenau Process for production of an abuse-proofed solid dosage form
US8323889B2 (en) 2004-07-01 2012-12-04 Gruenenthal Gmbh Process for the production of an abuse-proofed solid dosage form
US20080312264A1 (en) * 2004-07-01 2008-12-18 Grunenthal Gmbh Process for the production of an abuse-proofed solid dosage form
US20060039864A1 (en) * 2004-07-01 2006-02-23 Johannes Bartholomaus Abuse-proofed oral dosage form
US20180147149A1 (en) * 2004-07-01 2018-05-31 Grünenthal GmbH Abuse-proofed oral dosage form
US20160367549A1 (en) * 2004-07-01 2016-12-22 Grünenthal GmbH Abuse-proofed oral dosage form
US8114384B2 (en) 2004-07-01 2012-02-14 Gruenenthal Gmbh Process for the production of an abuse-proofed solid dosage form
US11844865B2 (en) 2004-07-01 2023-12-19 Grünenthal GmbH Abuse-proofed oral dosage form
US20140112984A1 (en) * 2005-02-04 2014-04-24 Gruenenthal Gmbh Crush resistant delayed-release dosage forms
US20080311187A1 (en) * 2005-02-04 2008-12-18 Grunenthal Gmbh Crush resistan delayed-release dosage form
US20180369235A1 (en) * 2005-02-04 2018-12-27 Grünenthal GmbH Crush resistant delayed-release dosage forms
US20100151028A1 (en) * 2005-02-04 2010-06-17 Grunenthal Gmbh Crush resistant delayed-release dosage forms
US20170312271A1 (en) * 2005-02-04 2017-11-02 Grünenthal GmbH Crush resistant delayed-release dosage forms
US10675278B2 (en) 2005-02-04 2020-06-09 Grünenthal GmbH Crush resistant delayed-release dosage forms
US10729658B2 (en) 2005-02-04 2020-08-04 Grünenthal GmbH Process for the production of an abuse-proofed dosage form
US20080311197A1 (en) * 2005-02-04 2008-12-18 Grunenthal Gmbh Process for the production of an abuse-proofed dosage form
US20140322311A1 (en) * 2005-02-04 2014-10-30 Grünenthal GmbH Crush resistan delayed-release dosage form
US20060188447A1 (en) * 2005-02-04 2006-08-24 Elisabeth Arkenau-Maric Process for the production of an abuse-proofed dosage form
US20060193914A1 (en) * 2005-02-04 2006-08-31 Judy Ashworth Crush resistant delayed-release dosage forms
US20070020335A1 (en) * 2005-07-07 2007-01-25 Farnam Companies, Inc. Sustained release pharmaceutical compositions for highly water soluble drugs
US8221792B2 (en) 2005-07-07 2012-07-17 Farnam Companies, Inc. Sustained release pharmaceutical compositions for highly water soluble drugs
US9125833B2 (en) 2005-11-02 2015-09-08 Relmada Therapeutics, Inc. Multimodal abuse resistant and extended release opioid formulations
US20100249045A1 (en) * 2005-11-02 2010-09-30 Theraquest Biosciences, Inc. Multimodal Abuse Resistant and Extended Release Opioid Formulations
US20080280975A1 (en) * 2005-11-02 2008-11-13 Theraquest Biosciences, Inc. Methods of preventing the serotonin syndrome and compositions for use thereof
US20100210732A1 (en) * 2005-11-02 2010-08-19 Najib Babul Methods of Preventing the Serotonin Syndrome and Compositions for Use Therefor
US8329744B2 (en) 2005-11-02 2012-12-11 Relmada Therapeutics, Inc. Methods of preventing the serotonin syndrome and compositions for use thereof
US20090317355A1 (en) * 2006-01-21 2009-12-24 Abbott Gmbh & Co. Kg, Abuse resistant melt extruded formulation having reduced alcohol interaction
US20100172989A1 (en) * 2006-01-21 2010-07-08 Abbott Laboratories Abuse resistant melt extruded formulation having reduced alcohol interaction
US20090082466A1 (en) * 2006-01-27 2009-03-26 Najib Babul Abuse Resistant and Extended Release Formulations and Method of Use Thereof
US20080075771A1 (en) * 2006-07-21 2008-03-27 Vaughn Jason M Hydrophilic opioid abuse deterrent delivery system using opioid antagonists
US20080075770A1 (en) * 2006-07-21 2008-03-27 Vaughn Jason M Hydrophilic abuse deterrent delivery system
US20080020032A1 (en) * 2006-07-21 2008-01-24 Michael Crowley Hydrophobic abuse deterrent delivery system for hydromorphone
US20080075768A1 (en) * 2006-07-21 2008-03-27 Vaughn Jason M Hydrophobic opioid abuse deterrent delivery system using opioid antagonists
US9095614B2 (en) 2006-08-25 2015-08-04 Purdue Pharma L.P. Tamper resistant dosage forms
US9763886B2 (en) 2006-08-25 2017-09-19 Purdue Pharma L.P. Tamper resistant dosage forms
US9492389B2 (en) 2006-08-25 2016-11-15 Purdue Pharma L.P. Tamper resistant dosage forms
US8911719B2 (en) 2006-08-25 2014-12-16 Purdue Pharma Lp Tamper resistant dosage forms
US8894988B2 (en) 2006-08-25 2014-11-25 Purdue Pharma L.P. Tamper resistant dosage forms
US9492390B2 (en) 2006-08-25 2016-11-15 Purdue Pharma L.P. Tamper resistant dosage forms
US8894987B2 (en) 2006-08-25 2014-11-25 William H. McKenna Tamper resistant dosage forms
US9492391B2 (en) 2006-08-25 2016-11-15 Purdue Pharma L.P. Tamper resistant dosage forms
US8846086B2 (en) 2006-08-25 2014-09-30 Purdue Pharma L.P. Tamper resistant dosage forms
US8834925B2 (en) 2006-08-25 2014-09-16 Purdue Pharma L.P. Tamper resistant dosage forms
US8821929B2 (en) 2006-08-25 2014-09-02 Purdue Pharma L.P. Tamper resistant dosage forms
US10076498B2 (en) 2006-08-25 2018-09-18 Purdue Pharma L.P. Tamper resistant dosage forms
US8815289B2 (en) 2006-08-25 2014-08-26 Purdue Pharma L.P. Tamper resistant dosage forms
US10076499B2 (en) 2006-08-25 2018-09-18 Purdue Pharma L.P. Tamper resistant dosage forms
US9492392B2 (en) 2006-08-25 2016-11-15 Purdue Pharma L.P. Tamper resistant dosage forms
US9084816B2 (en) 2006-08-25 2015-07-21 Purdue Pharma L.P. Tamper resistant dosage forms
US9095615B2 (en) 2006-08-25 2015-08-04 Purdue Pharma L.P. Tamper resistant dosage forms
US9486413B2 (en) 2006-08-25 2016-11-08 Purdue Pharma L.P. Tamper resistant dosage forms
US9101661B2 (en) 2006-08-25 2015-08-11 Purdue Pharma L.P. Tamper resistant dosage forms
US20090081290A1 (en) * 2006-08-25 2009-03-26 Purdue Pharma L.P. Tamper resistant dosage forms
US9763933B2 (en) 2006-08-25 2017-09-19 Purdue Pharma L.P. Tamper resistant dosage forms
US9492393B2 (en) 2006-08-25 2016-11-15 Purdue Pharma L.P. Tamper resistant dosage forms
US9770416B2 (en) 2006-08-25 2017-09-26 Purdue Pharma L.P. Tamper resistant dosage forms
US9770417B2 (en) 2006-08-25 2017-09-26 Purdue Pharma L.P. Tamper resistant dosage forms
US9545380B2 (en) 2006-08-25 2017-01-17 Purdue Pharma L.P. Tamper resistant dosage forms
US11298322B2 (en) 2006-08-25 2022-04-12 Purdue Pharma L.P. Tamper resistant dosage forms
US11304908B2 (en) 2006-08-25 2022-04-19 Purdue Pharma L.P. Tamper resistant dosage forms
US11304909B2 (en) 2006-08-25 2022-04-19 Purdue Pharma L.P. Tamper resistant dosage forms
US9775810B2 (en) 2006-08-25 2017-10-03 Purdue Pharma L.P. Tamper resistant dosage forms
US11826472B2 (en) 2006-08-25 2023-11-28 Purdue Pharma L.P. Tamper resistant dosage forms
US9775811B2 (en) 2006-08-25 2017-10-03 Purdue Pharma L.P. Tamper resistant dosage forms
US11904055B2 (en) 2006-08-25 2024-02-20 Purdue Pharma L.P. Tamper resistant dosage forms
US11938225B2 (en) 2006-08-25 2024-03-26 Purdue Pharm L.P. Tamper resistant dosage forms
US9775809B2 (en) 2006-08-25 2017-10-03 Purdue Pharma L.P. Tamper resistant dosage forms
US9775812B2 (en) 2006-08-25 2017-10-03 Purdue Pharma L.P. Tamper resistant dosage forms
US9775808B2 (en) 2006-08-25 2017-10-03 Purdue Pharma L.P. Tamper resistant dosage forms
US9486412B2 (en) 2006-08-25 2016-11-08 Purdue Pharma L.P. Tamper resistant dosage forms
US8722086B2 (en) * 2007-03-07 2014-05-13 Gruenenthal Gmbh Dosage form with impeded abuse
US20090004267A1 (en) * 2007-03-07 2009-01-01 Gruenenthal Gmbh Dosage Form with Impeded Abuse
US20080292665A1 (en) * 2007-05-25 2008-11-27 Kulli John C Simple mechanical procedure and product for deterring substance abuse
US9642809B2 (en) 2007-06-04 2017-05-09 Egalet Ltd. Controlled release pharmaceutical compositions for prolonged effect
US20090022798A1 (en) * 2007-07-20 2009-01-22 Abbott Gmbh & Co. Kg Formulations of nonopioid and confined opioid analgesics
US20100181705A1 (en) * 2007-08-17 2010-07-22 Grunenthal Gmbh Star distributor
US8894904B2 (en) 2007-08-17 2014-11-25 Gruenenthal Gmbh Star distributor
US8691270B2 (en) 2007-12-17 2014-04-08 Paladin Labs Inc. Misuse preventative, controlled release formulation
US8920834B2 (en) 2007-12-17 2014-12-30 Paladin Labs Inc. Misuse preventative, controlled release formulation
US8920833B2 (en) 2007-12-17 2014-12-30 Paladin Labs Inc. Misuse preventative, controlled release formulation
EP2219612A4 (en) * 2007-12-17 2013-10-30 Paladin Labs Inc Misuse preventative, controlled release formulation
US20090175937A1 (en) * 2007-12-17 2009-07-09 Labopharm, Inc. Misuse Preventative, Controlled Release Formulation
US8486448B2 (en) 2007-12-17 2013-07-16 Paladin Labs Inc. Misuse preventative, controlled release formulation
US9750701B2 (en) 2008-01-25 2017-09-05 Grünenthal GmbH Pharmaceutical dosage form
RU2493830C2 (en) * 2008-01-25 2013-09-27 Грюненталь Гмбх Drug form
AU2009207796B2 (en) * 2008-01-25 2014-03-27 Grunenthal Gmbh Pharmaceutical dosage form
US8383152B2 (en) * 2008-01-25 2013-02-26 Gruenenthal Gmbh Pharmaceutical dosage form
US20090202634A1 (en) * 2008-01-25 2009-08-13 Grunenthal Gmbh Pharmaceutical dosage form
TWI454288B (en) * 2008-01-25 2014-10-01 Gruenenthal Chemie Pharmaceutical dosage form
WO2009092601A1 (en) * 2008-01-25 2009-07-30 Grünenthal GmbH Pharmaceutical dosage form
KR101616246B1 (en) * 2008-01-25 2016-05-02 그뤼넨탈 게엠베하 Pharmaceutical dosage form
US9226907B2 (en) 2008-02-01 2016-01-05 Abbvie Inc. Extended release hydrocodone acetaminophen and related methods and uses thereof
US8394408B2 (en) 2008-03-11 2013-03-12 Depomed, Inc. Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic
US8668929B2 (en) 2008-03-11 2014-03-11 Depomed, Inc. Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic
US8377453B2 (en) 2008-03-11 2013-02-19 Depomed, Inc. Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic
US8372432B2 (en) 2008-03-11 2013-02-12 Depomed, Inc. Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic
US20100015222A1 (en) * 2008-03-11 2010-01-21 Depomed, Inc. Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic
US20100196474A1 (en) * 2008-03-11 2010-08-05 Depomed, Inc. Gastric Retentive Extended-Release Dosage Forms Comprising Combinations of a Non-Opioid Analgesic and an Opioid Analgesic
US20110082214A1 (en) * 2008-05-09 2011-04-07 Gruenthal Gmbh Process for the preparation of a solid dosage form, in particular a tablet, for pharmaceutical use and process for the preparation of a precursor for a solid dosage form, in particular a tablet
US9161917B2 (en) 2008-05-09 2015-10-20 Grünenthal GmbH Process for the preparation of a solid dosage form, in particular a tablet, for pharmaceutical use and process for the preparation of a precursor for a solid dosage form, in particular a tablet
EA020030B1 (en) * 2008-07-08 2014-08-29 Алсиано А/С Chewing gum compositions and method of preparing same
WO2010003425A1 (en) * 2008-07-08 2010-01-14 Alsiano A/S Powdered chewing gum compositions, the use thereof and a method of preparing such compositions
US20110117173A1 (en) * 2008-07-08 2011-05-19 Alsiano A/S Powdered chewing gum compositions, the use thereof and a method of preparing such compositions
EP2143336A1 (en) * 2008-07-08 2010-01-13 Alsiano A/S Powdered chewing gum compositions, the use thereof and a method for preparing such compositions
US8460640B2 (en) 2008-12-12 2013-06-11 Paladin Labs, Inc. Narcotic drug formulations with decreased abuse potential
US20110237615A1 (en) * 2008-12-12 2011-09-29 Paladin Labs Inc. Narcotic Drug Formulations with Decreased Abuse Potential
US8486449B2 (en) 2008-12-16 2013-07-16 Paladin Labs Inc. Misuse preventative, controlled release formulation
US20100239662A1 (en) * 2008-12-16 2010-09-23 Miloud Rahmouni Misuse preventative, controlled release formulation
US8927014B2 (en) 2008-12-16 2015-01-06 Paladin Labs Inc. Misuse preventative, controlled release formulation
US8927013B2 (en) 2008-12-16 2015-01-06 Paladin Labs Inc. Misuse preventative, controlled release formulation
US8685447B2 (en) 2008-12-16 2014-04-01 Paladin Labs Inc. Misuse preventative, controlled release formulation
US9358295B2 (en) 2009-02-06 2016-06-07 Egalet Ltd. Immediate release composition resistant to abuse by intake of alcohol
US9005660B2 (en) 2009-02-06 2015-04-14 Egalet Ltd. Immediate release composition resistant to abuse by intake of alcohol
US9023394B2 (en) 2009-06-24 2015-05-05 Egalet Ltd. Formulations and methods for the controlled release of active drug substances
WO2010151741A1 (en) * 2009-06-25 2010-12-29 Elite Laboratories, Inc. Abuse resistant oral dosage forms
US10213388B2 (en) 2009-06-25 2019-02-26 Elite Laboratories, Inc. Abuse resistant oral dosage forms
US9056054B2 (en) * 2009-06-25 2015-06-16 Elite Laboratories, Inc. Abuse resistant oral dosage forms
US20110020451A1 (en) * 2009-07-22 2011-01-27 Grunenthal Gmbh Tamper-resistant dosage form for oxidation-sensitive opioids
US9925146B2 (en) 2009-07-22 2018-03-27 Grünenthal GmbH Oxidation-stabilized tamper-resistant dosage form
US10080721B2 (en) 2009-07-22 2018-09-25 Gruenenthal Gmbh Hot-melt extruded pharmaceutical dosage form
US10493033B2 (en) 2009-07-22 2019-12-03 Grünenthal GmbH Oxidation-stabilized tamper-resistant dosage form
US20110052685A1 (en) * 2009-08-31 2011-03-03 Depomed, Inc. Gastric retentive pharmaceutical compositions for immediate and extended release of acetaminophen
US10668060B2 (en) 2009-12-10 2020-06-02 Collegium Pharmaceutical, Inc. Tamper-resistant pharmaceutical compositions of opioids and other drugs
US9198861B2 (en) 2009-12-22 2015-12-01 Mallinckrodt Llc Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans
US8597681B2 (en) 2009-12-22 2013-12-03 Mallinckrodt Llc Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans
US20110187017A1 (en) * 2010-02-03 2011-08-04 Grunenthal Gmbh Preparation of a powdery pharmaceutical composition by means of an extruder
US9579285B2 (en) 2010-02-03 2017-02-28 Gruenenthal Gmbh Preparation of a powdery pharmaceutical composition by means of an extruder
US10300141B2 (en) 2010-09-02 2019-05-28 Grünenthal GmbH Tamper resistant dosage form comprising inorganic salt
US9636303B2 (en) 2010-09-02 2017-05-02 Gruenenthal Gmbh Tamper resistant dosage form comprising an anionic polymer
US9872837B2 (en) 2010-12-22 2018-01-23 Purdue Pharma L.P. Tamper resistant controlled release dosage forms
US10966932B2 (en) 2010-12-22 2021-04-06 Purdue Pharma L.P. Encased tamper resistant controlled release dosage forms
US9572779B2 (en) 2010-12-22 2017-02-21 Purdue Pharma L.P. Encased tamper resistant controlled release dosage forms
US11590082B2 (en) 2010-12-22 2023-02-28 Purdue Pharma L.P. Encased tamper resistant controlled release dosage forms
US11911512B2 (en) 2010-12-22 2024-02-27 Purdue Pharma L.P. Encased tamper resistant controlled release dosage forms
US9393206B2 (en) 2010-12-22 2016-07-19 Purdue Pharma L.P. Encased tamper resistant controlled release dosage forms
US8808740B2 (en) 2010-12-22 2014-08-19 Purdue Pharma L.P. Encased tamper resistant controlled release dosage forms
US9750703B2 (en) 2010-12-22 2017-09-05 Purdue Pharma L.P. Encased tamper resistant controlled release dosage forms
US9744136B2 (en) 2010-12-22 2017-08-29 Purdue Pharma L.P. Encased tamper resistant controlled release dosage forms
US9861584B2 (en) 2010-12-22 2018-01-09 Purdue Pharma L.P. Tamper resistant controlled release dosage forms
US9707180B2 (en) 2010-12-23 2017-07-18 Purdue Pharma L.P. Methods of preparing tamper resistant solid oral dosage forms
US9895317B2 (en) 2010-12-23 2018-02-20 Purdue Pharma L.P. Tamper resistant solid oral dosage forms
US9233073B2 (en) 2010-12-23 2016-01-12 Purdue Pharma L.P. Tamper resistant solid oral dosage forms
US9629837B2 (en) 2011-05-17 2017-04-25 Mallinckrodt Llc Pharmaceutical compositions for extended release of oxycodone and acetaminophen resulting in a quick onset and prolonged period of analgesia
US9539328B2 (en) 2011-05-17 2017-01-10 Mallinckrodt Llc Tamper resistant composition comprising hydrocodone and acetaminophen for rapid onset and extended duration of analgesia
US8658631B1 (en) 2011-05-17 2014-02-25 Mallinckrodt Llc Combination composition comprising oxycodone and acetaminophen for rapid onset and extended duration of analgesia
US8741885B1 (en) 2011-05-17 2014-06-03 Mallinckrodt Llc Gastric retentive extended release pharmaceutical compositions
US9050335B1 (en) 2011-05-17 2015-06-09 Mallinckrodt Llc Pharmaceutical compositions for extended release of oxycodone and acetaminophen resulting in a quick onset and prolonged period of analgesia
US9468636B2 (en) 2011-05-17 2016-10-18 Mallinckrodt Llc Combination composition comprising oxycodone and acetaminophen for rapid onset and extended duration of analgesia
US8858963B1 (en) 2011-05-17 2014-10-14 Mallinckrodt Llc Tamper resistant composition comprising hydrocodone and acetaminophen for rapid onset and extended duration of analgesia
US9433582B2 (en) 2011-05-17 2016-09-06 Mallinckrodt Llc Gastric retentive extended release pharmaceutical compositions
US10864164B2 (en) 2011-07-29 2020-12-15 Grünenthal GmbH Tamper-resistant tablet providing immediate drug release
US10201502B2 (en) 2011-07-29 2019-02-12 Gruenenthal Gmbh Tamper-resistant tablet providing immediate drug release
US10695297B2 (en) 2011-07-29 2020-06-30 Grünenthal GmbH Tamper-resistant tablet providing immediate drug release
US9655853B2 (en) 2012-02-28 2017-05-23 Grünenthal GmbH Tamper-resistant dosage form comprising pharmacologically active compound and anionic polymer
US10335373B2 (en) 2012-04-18 2019-07-02 Grunenthal Gmbh Tamper resistant and dose-dumping resistant pharmaceutical dosage form
US9993422B2 (en) 2012-04-18 2018-06-12 SpecGx LLC Immediate release, abuse deterrent pharmaceutical compositions
AU2013257943B2 (en) * 2012-05-11 2017-10-05 Grünenthal GmbH Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc
EA029171B1 (en) * 2012-05-11 2018-02-28 Грюненталь Гмбх Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc and process for manufacture thereof
US10064945B2 (en) * 2012-05-11 2018-09-04 Gruenenthal Gmbh Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc
WO2013167735A1 (en) 2012-05-11 2013-11-14 Grünenthal GmbH Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc
US9044402B2 (en) 2012-07-06 2015-06-02 Egalet Ltd. Abuse-deterrent pharmaceutical compositions for controlled release
US11096887B2 (en) 2012-07-12 2021-08-24 SpecGx LLC Extended release, abuse deterrent pharmaceutical compositions
US9730885B2 (en) 2012-07-12 2017-08-15 Mallinckrodt Llc Extended release, abuse deterrent pharmaceutical compositions
US10485753B2 (en) 2012-07-12 2019-11-26 SpecGx LLC Extended release, abuse deterrent pharmaceutical compositions
US9545448B2 (en) 2013-02-05 2017-01-17 Purdue Pharma L.P. Tamper resistant pharmaceutical formulations
US10478504B2 (en) 2013-02-05 2019-11-19 Purdue Pharma L.P. Tamper resistant pharmaceutical formulations
US9662399B2 (en) 2013-02-05 2017-05-30 Purdue Pharma L.P. Tamper resistant pharmaceutical formulations
US9655971B2 (en) 2013-02-05 2017-05-23 Purdue Pharma L.P. Tamper resistant pharmaceutical formulations
US11576974B2 (en) 2013-02-05 2023-02-14 Purdue Pharma L.P. Tamper resistant pharmaceutical formulations
US9149533B2 (en) 2013-02-05 2015-10-06 Purdue Pharma L.P. Tamper resistant pharmaceutical formulations
US10792364B2 (en) 2013-02-05 2020-10-06 Purdue Pharma L.P. Tamper resistant pharmaceutical formulations
US9579389B2 (en) 2013-02-05 2017-02-28 Purdue Pharma L.P. Methods of preparing tamper resistant pharmaceutical formulations
US10195152B2 (en) 2013-03-15 2019-02-05 Purdue Pharma L.P. Tamper resistant pharmaceutical formulations
US10517832B2 (en) 2013-03-15 2019-12-31 Purdue Pharma L.P. Tamper resistant pharmaceutical formulations
US10751287B2 (en) 2013-03-15 2020-08-25 Purdue Pharma L.P. Tamper resistant pharmaceutical formulations
US9301918B2 (en) 2013-03-15 2016-04-05 Mallinckrodt Llc Abuse deterrent solid dosage form for immediate release with functional score
US9616030B2 (en) 2013-03-15 2017-04-11 Purdue Pharma L.P. Tamper resistant pharmaceutical formulations
US10154966B2 (en) 2013-05-29 2018-12-18 Grünenthal GmbH Tamper-resistant dosage form containing one or more particles
US9737490B2 (en) 2013-05-29 2017-08-22 Grünenthal GmbH Tamper resistant dosage form with bimodal release profile
US10624862B2 (en) 2013-07-12 2020-04-21 Grünenthal GmbH Tamper-resistant dosage form containing ethylene-vinyl acetate polymer
US10449547B2 (en) 2013-11-26 2019-10-22 Grünenthal GmbH Preparation of a powdery pharmaceutical composition by means of cryo-milling
US9913814B2 (en) 2014-05-12 2018-03-13 Grünenthal GmbH Tamper resistant immediate release capsule formulation comprising tapentadol
US9872835B2 (en) 2014-05-26 2018-01-23 Grünenthal GmbH Multiparticles safeguarded against ethanolic dose-dumping
US11583493B2 (en) 2014-07-03 2023-02-21 SpecGx LLC Abuse deterrent immediate release formulations comprising non-cellulose polysaccharides
US11617712B2 (en) 2014-07-03 2023-04-04 SpecGx LLC Abuse deterrent immediate release formulations comprising non-cellulose polysaccharides
US11517521B2 (en) 2014-07-03 2022-12-06 SpecGx LLC Abuse deterrent immediate release formulations comprising non-cellulose polysaccharides
US9855263B2 (en) 2015-04-24 2018-01-02 Grünenthal GmbH Tamper-resistant dosage form with immediate release and resistance against solvent extraction
US10842750B2 (en) 2015-09-10 2020-11-24 Grünenthal GmbH Protecting oral overdose with abuse deterrent immediate release formulations
US10646485B2 (en) 2016-06-23 2020-05-12 Collegium Pharmaceutical, Inc. Process of making stable abuse-deterrent oral formulations
US10632201B2 (en) 2017-10-19 2020-04-28 Capsugel Belgium Nv Immediate release abuse deterrent formulations
US11478426B2 (en) 2018-09-25 2022-10-25 SpecGx LLC Abuse deterrent immediate release capsule dosage forms

Also Published As

Publication number Publication date
CN101027044B (en) 2012-01-11
CN101027044A (en) 2007-08-29
RU2007103707A (en) 2008-11-20
ES2402192T5 (en) 2023-04-12
SI1765303T1 (en) 2013-03-29
US20080248113A1 (en) 2008-10-09
US20200038330A1 (en) 2020-02-06
US20130251643A1 (en) 2013-09-26
US20170209378A9 (en) 2017-07-27
US20160175256A1 (en) 2016-06-23
US20180147149A1 (en) 2018-05-31
CY1113847T1 (en) 2016-07-27
US20140112989A1 (en) 2014-04-24
US20160367549A1 (en) 2016-12-22
US20160184295A1 (en) 2016-06-30
US20200397704A1 (en) 2020-12-24
IL180470A0 (en) 2007-06-03
DE102004032049A1 (en) 2006-01-19
RU2396944C2 (en) 2010-08-20
DK1765303T4 (en) 2023-01-30
SI1765303T2 (en) 2023-03-31
US11844865B2 (en) 2023-12-19
HK1107930A1 (en) 2008-04-25
DK1765303T3 (en) 2013-03-25
PE20060523A1 (en) 2006-08-25
PT1765303E (en) 2013-04-02
ES2402192T3 (en) 2013-04-29
MX2007000009A (en) 2007-03-07
US20150313845A1 (en) 2015-11-05

Similar Documents

Publication Publication Date Title
US11844865B2 (en) Abuse-proofed oral dosage form
AU2005259476B2 (en) Oral dosage form safeguarded against abuse
US20200009082A1 (en) Abuse-proofed oral dosage form
US8323889B2 (en) Process for the production of an abuse-proofed solid dosage form
AU2005259478B2 (en) Oral dosage form safeguarded against abuse containing (1R, 2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol

Legal Events

Date Code Title Description
AS Assignment

Owner name: GRUNENTHAL GMBH, GERMANY

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BARTHOLOMAUS, JOHANNES DR.;KUGELMANN, HEINRICH;REEL/FRAME:015983/0192

Effective date: 20041109

AS Assignment

Owner name: GRUNENTHAL GMBH, GERMANY

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ARKENAU-MARIC, ELISABETH DR.;REEL/FRAME:017911/0040

Effective date: 20060510

AS Assignment

Owner name: JPMORGAN CHASE BANK, N.A., AS ADMINISTRATIVE AGENT

Free format text: CONFIRMATORY GRANT OF SECURITY INTEREST IN UNITED STATES PATENTS (EXCLUSIVELY LICENSED PATENTS);ASSIGNOR:ENDO PHARMACEUTICALS INC.;REEL/FRAME:025456/0172

Effective date: 20101130

AS Assignment

Owner name: MORGAN STANLEY SENIOR FUNDING, INC., AS ADMINISTRA

Free format text: SECURITY INTEREST IN EXCLUSIVELY LICENSED PATENTS;ASSIGNOR:ENDO PHARMACEUTICALS INC.;REEL/FRAME:026561/0978

Effective date: 20110617

AS Assignment

Owner name: ENDO PHARMACEUTICALS INC., PENNSYLVANIA

Free format text: RELEASE OF SECURITY INTEREST IN EXCLUSIVELY LICENSED PATENTS RECORDED AT REEL/FRAME 25456/172;ASSIGNOR:JPMORGAN CHASE BANK N.A., AS ADMINISTRATIVE AGENT;REEL/FRAME:026577/0357

Effective date: 20110617

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION

AS Assignment

Owner name: ENDO PHARMACEUTICALS SOLUTIONS INC., PENNSYLVANIA

Free format text: RELEASE OF PATENT SECURITY INTEREST IN EXCLUSIVELY LICENSED PATENTS;ASSIGNOR:MORGAN STANLEY SENIOR FUNDING, INC., AS ADMINISTRATIVE AGENT;REEL/FRAME:032380/0157

Effective date: 20140228

AS Assignment

Owner name: DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AG

Free format text: GRANT OF SECURITY INTEREST IN LICENSED PATENTS;ASSIGNOR:ENDO PHARMACEUTICALS, INC.;REEL/FRAME:032491/0620

Effective date: 20140228

AS Assignment

Owner name: ENDO PHARMACEUTICALS INC., PENNSYLVANIA

Free format text: CORRECTIVE ASSIGNMENT TO CORRECT THE NAME OF RECEIVING PARTY IN RELEASE OF PATENT SECURITY INTEREST IN EXCLUSIVELY LICENSED PATENTS PREVIOUSLY RECORDED ON REEL 032380 FRAME 0157. ASSIGNOR(S) HEREBY CONFIRMS THE RELEASE OF SECURITY INTEREST IN EXCLUSIVELY LICENSED PATENTS.;ASSIGNOR:MORGAN STANLEY SENIOR FUNDING, INC., AS ADMINISTRATIVE AGENT;REEL/FRAME:032513/0255

Effective date: 20140228

AS Assignment

Owner name: ENDO PHARMACEUTICALS, INC., PENNSYLVANIA

Free format text: RELEASE BY SECURED PARTY;ASSIGNOR:DEUTSCHE BANK AG NEW YORK BRANCH;REEL/FRAME:042362/0001

Effective date: 20170427

Owner name: ASTORA WOMEN'S HEALTH HOLDINGS, LLC, PENNSYLVANIA

Free format text: RELEASE BY SECURED PARTY;ASSIGNOR:DEUTSCHE BANK AG NEW YORK BRANCH;REEL/FRAME:042362/0001

Effective date: 20170427

Owner name: ENDO PHARMACEUTICALS SOLUTIONS, INC., PENNSYLVANIA

Free format text: RELEASE BY SECURED PARTY;ASSIGNOR:DEUTSCHE BANK AG NEW YORK BRANCH;REEL/FRAME:042362/0001

Effective date: 20170427