US20100260833A1 - Abuse-proofed dosage form - Google Patents

Abuse-proofed dosage form Download PDF

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Publication number
US20100260833A1
US20100260833A1 US12/822,719 US82271910A US2010260833A1 US 20100260833 A1 US20100260833 A1 US 20100260833A1 US 82271910 A US82271910 A US 82271910A US 2010260833 A1 US2010260833 A1 US 2010260833A1
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US
United States
Prior art keywords
methyl
chloro
benzodiazepin
phenyl
dosage form
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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
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US12/822,719
Inventor
Johannes Bartholomäus
Heinrich Kugelmann
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Gruenenthal GmbH
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Gruenenthal GmbH
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Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=34743222&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=US20100260833(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from DE10250083A external-priority patent/DE10250083A1/en
Priority to US12/822,719 priority Critical patent/US20100260833A1/en
Application filed by Gruenenthal GmbH filed Critical Gruenenthal GmbH
Publication of US20100260833A1 publication Critical patent/US20100260833A1/en
Priority to US13/365,742 priority patent/US20120135071A1/en
Priority to US13/572,926 priority patent/US20120308654A1/en
Priority to US13/803,789 priority patent/US20130195935A1/en
Priority to US14/069,439 priority patent/US20140093559A1/en
Priority to US14/527,911 priority patent/US20150056147A1/en
Priority to US15/245,424 priority patent/US9675610B2/en
Priority to US15/587,501 priority patent/US20170239185A1/en
Priority to US16/032,533 priority patent/US10369109B2/en
Priority to US16/434,306 priority patent/US20190282506A1/en
Priority to US16/994,867 priority patent/US20200375905A1/en
Abandoned legal-status Critical Current

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    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • 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
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • A61K9/2009—Inorganic compounds
    • 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
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds
    • 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
    • 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
    • A61P25/26—Psychostimulants, e.g. nicotine, cocaine

Definitions

  • the present invention relates to a solid dosage form with reduced parenteral abuse containing, in addition to one or more active ingredients with potential for abuse, at least one viscosity-increasing agent in quantities such that, on extraction with the assistance of a necessary minimum quantity of aqueous liquid, a gel is formed which can still preferably pass through a needle, which gel, however, remains visually distinguishable even after being introduced into a further quantity of an aqueous liquid.
  • the corresponding dosage forms are comminuted, for example ground, by the abuser and the active ingredient is extracted from the powder obtained by comminution of the dosage form with the assistance of a preferably aqueous liquid, preferably the minimum quantity necessary, and the resultant solution, optionally after filtration through cotton wool or cellulose wadding, is administered parenterally, in particular intravenously.
  • parenteral administration due to this parenteral administration, only the smallest possible quantities of an aqueous liquid are used for extraction, in particular so as to obtain the smallest possible injection volume with active ingredient which results in the desired rapid rush or “kick”. In this manner, parenteral administration, in comparison with oral administration, tends to give rise to an accelerated rise in levels of the active ingredient providing the abuser with the desired result.
  • a corresponding approach to the prevention of parenteral abuse also underlies the multilayer tablet disclosed in WO 95/20947 which contains the active ingredient with potential for abuse and one or more gel formers each in different layers.
  • the viscosity-increasing agents are added in quantities such that the corresponding gel cannot be administered with the assistance of conventional hypodermic needles.
  • the object of the present invention was to provide a dosage form with at least reduced potential for abuse for active ingredients having with such potential, which dosage form prevents any preferably still possible parenteral, in particular intravenous, abuse of the active ingredients.
  • the solid dosage form according to the invention with at least reduced potential for parenteral abuse, which dosage form, in addition to one or more active ingredients with potential for abuse, comprises at least one viscosity-increasing agent in a quantity such that a gel which may preferably still pass through a needle is formed in an extract obtained from the dosage form with the assistance of a necessary minimum quantity of an aqueous liquid, which gel remains visually distinguishable when introduced into a further quantity of an aqueous liquid.
  • visually distinguishable means that the active ingredient-containing gel formed by extraction from the dosage form with the assistance of a necessary minimum quantity of aqueous liquid, when introduced with a hypodermic needle with a diameter of 0.9 mm 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 min.
  • the increase in viscosity of the gel with the assistance of the selected viscosity-increasing agent means that, although this has been rendered more difficult, the gel may still be passed through a needle or injected. It also means that when the resultant extract or gel is introduced at 37° C. into a further quantity of aqueous liquid, for example also by injection into blood, a largely cohesive thread is initially obtained which, while it may be broken up into smaller fragments by mechanical action, it cannot be dispersed or even dissolved in such a manner that it may safely be administered parenterally, in particular intravenously.
  • Intravenous administration of such an extract would most probably result in obstruction of blood vessels, associated with serious embolism or even death of the abuser.
  • an extract or gel obtained from the dosage form according to the invention with the assistance of a necessary minimum quantity of an aqueous liquid, preferably water, is deemed to be passable through a needle if the gel formed in this manner can still be drawn up and injected back out of a hypodermic needle with a diameter of 2 mm, preferably of 1.5 mm, particularly preferably of 0.6 mm.
  • compositions with potential for abuse are known to the person skilled in the art, as are the quantities 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 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 dosage form according to the invention is also suitable for the administration of a plurality of active ingredients. It is preferably used for the administration of a single active ingredient.
  • the dosage form according to the invention is in particular suitable for preventing abuse of a pharmaceutical active ingredient selected from the group consisting of opiates, opioids, tranquillisers, preferably benzodiazepines, stimulants and other narcotics.
  • a pharmaceutical active ingredient selected from the group consisting of opiates, opioids, tranquillisers, preferably benzodiazepines, stimulants and other narcotics.
  • the dosage form according to the invention is very particularly preferably suitable for preventing abuse of an opiate, opioid, tranquilliser or another narcotic, which is selected from the group consisting of N- ⁇ 1-[2-(4-Ethyl-5-oxo-2-tetrazolin-1-yl)ethyl]-4-methoxymethyl-4-piperidyl ⁇ propionanilide (alfentanil), 5,5-diallylbarbituric acid (allobarbital), allylprodine, alphaprodine, 8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]-benzodiazepine (alprazolam), 2-diethylaminopropiophenone (amfepramone), ( ⁇ )-a-methylphenethylamine (amphetamine), 2-(a-methylphenethylamino)-2-phenylacetonitrile (amphetaminil), 5-e
  • a viscosity-increasing agent is suitable for use in the dosage form according to the invention.
  • said agent is first formulated in a corresponding dosage form in quantities such that there is no appreciable ( ⁇ 5%) influence on active ingredient release relative to a dosage form without viscosity-increasing agent.
  • the corresponding dosage form is moreover comminuted, preferably ground, and extracted with 10 ml water at 25° C. If a gel is furthermore formed which meets the above-stated conditions, the corresponding viscosity-increasing agent is suitable for the production of a dosage form according to the invention.
  • one or more viscosity-increasing agents are used in the dosage form according to the invention, said agents being selected from the group consisting of microcrystalline cellulose with 11 wt. % carboxymethylcellulose sodium (Avicel® RC 591), carboxymethylcellulose sodium (Blanose®, CMC-Na C3001P®, 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 2611-75®), iota-carrage
  • a quantity of 0.1 to 25 wt. %, preferably of 0.5 to 15 wt. %, particularly preferably of 1-10 wt. % of the viscosity-increasing agent, relative to the total formulation, is sufficient in order to meet the above-stated conditions.
  • the viscosity-increasing agents used are those which, in addition to the above-stated conditions, also form a gel which encloses air bubbles on extraction from the dosage form with the necessary minimum quantity of aqueous liquid.
  • 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 active ingredient or ingredients with potential for abuse and the viscosity-increasing agents and optionally physiologically acceptable auxiliary substances may be formulated to yield the dosage form according to the invention in accordance with conventional methods known to the person skilled in the art.
  • Corresponding methods for formulating the dosage form according to the invention are known per se 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 inventive selection of the viscosity-increasing agents it is possible to combine the active ingredients and the viscosity-increasing agents in the dosage form according to the invention without spatial separation from one another, without there being any impairment of release of the active ingredient from the correctly administered dosage form relative to a corresponding dosage form which does not comprise the viscosity-increasing agent.
  • parenteral abuse-proofed solid dosage forms according to the invention are preferably suitable for oral or rectal administration, particularly preferably for oral administration.
  • the dosage form according to the invention is intended for rectal administration, it preferably assumes the form of a suppository.
  • the dosage form according to the invention is intended for oral administration, it preferably assumes the form of a tablet, a capsule or of an oral osmotic therapeutic system (OROS).
  • OROS oral osmotic therapeutic system
  • Oral osmotic therapeutic systems and suitable materials and processes for the production thereof are known per se to the person skilled in the art, for example 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.
  • the corresponding oral osmotic therapeutic system may preferably assume the form of a single or twin chamber system, in each case with a single layer or multilayer structure.
  • the push layer i.e. the layer which produces the osmotic pressure by swelling, by means of which the overlying layer is expelled from the system, preferably at least in part consists of the viscosity-increasing agents used according to the invention.
  • the orally administrable dosage form according to the invention assumes multiparticulate form containing in each case the complete mixture of active ingredient and viscosity-increasing agent, preferably in the form of microtablets, microcapsules, micropellets, granules, spheroids, beads or pellets, preferably packaged in capsules or press-moulded into tablets.
  • the multiparticulate forms preferably have a size in the range from 0.1 to 3 mm, particularly preferably in the range from 0.5 to 2 mm.
  • the dosage form according to the invention may preferably also comprise one or more active ingredients, blended with the viscosity-increasing agent, at least in part in delayed-release form, wherein delayed release may be achieved with the assistance of conventional materials and processes known to the person skilled in the art, for example by embedding the active ingredient in a delayed-release matrix or by applying one or more delayed-release coatings.
  • Delayed release of the active ingredient may preferably also be achieved by purposeful selection of one or more of the above-stated viscosity-increasing agents in suitable quantities as the matrix material.
  • the person skilled in the art may determine the agents and the quantity thereof suitable for the particular desired release by simple preliminary testing, wherein it must, of course, be ensured that, as described above, gel formation occurs when the attempt is made to abuse the resultant dosage form.
  • the delayed-release auxiliary substances and likewise further optionally present auxiliary substances, do not interfere with gel formation or impair the stability of the gel which is formed.
  • the dosage form according to the invention may also comprise a coating which is resistant to gastric juices and dissolves as a function of the pH value of the release environment.
  • the coating which is resistant to gastric juices preferably dissolves at a pH value of between 5 and 7.5.
  • the dosage form according to the invention contains the active ingredient not only in its delayed-release form, but also in its non-delayed-release form.
  • the active ingredient By combination with the immediately released active ingredient, it is possible to obtain an initial dose for rapid pain relief.
  • the slow release from the delayed-release form then prevents any rapid decline in action.
  • Example 2 One of the tablets was ground and shaken with 10 ml of water. A viscous, turbid suspension with enclosed air bubbles formed, the viscosity of which was greater than in Example 1. Once the coarse, solid components of the suspension had settled out, the gel which had formed was drawn up into a syringe with a 0.9 mm diameter needle. The drawn up gel was injected into water at 37° C. and threads, which did not mix with the water, with the diameter of the needle were clearly discernible. While the threads could be broken up by stirring, they could not be dissolved and the thread fragments remained visible to the naked eye. Were such a gel to be injected into blood vessels, vessel blockages would occur.
  • Example 8 9 10 11 12 13 Morphine sulfate 60 mg 60 mg 60 mg 60 mg 60 mg 60 mg pentahydrate Hydroxypropylmethylcellulose 60 mg 60 mg 60 mg 60 mg 60 mg 60 mg (Metolose 90 SH 15,000 from Shinetsu), 15,000 mPa ⁇ s Xanthan, NF 10 mg 30 mg Carboxymethylcellulose 10 mg (Tylose C300) Carboxymethylcellulose 10 mg (Tylose C600) Hydroxyethylcellulose (Tylose 10 mg H300) Hydroxyethylcellulose (Tylose 10 mg H4000) Microcrystalline cellulose 123 mg 123 mg 123 mg 123 mg 123 mg 123 mg 123 mg 123 mg (Avicel PH 102 from FMC) Highly disperse silicon dioxide 4 mg 4 mg 4 mg 4 mg 4 mg Magnesium stearate 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg
  • Example 14 15 16 17 18 Morphine sulfate pentahydrate 20 mg 20 mg 20 mg 20 mg 20 mg 20 mg 20 mg Xanthan, NF 10 mg Carboxymethylcellulose (Tylose C300) 10 mg Carboxymethylcellulose (Tylose C600) 10 mg Hydroxyethylcellulose (Tylose H300) 10 mg Hydroxyethylcellulose (Tylose H4000) 10 mg Microcrystalline cellulose (Avicel PH 102 68 mg 68 mg 68 mg 68 mg 68 mg from FMC) Highly disperse silicon dioxide 1 mg 1 mg 1 mg 1 mg 1 mg 1 mg Magnesium stearate 1 mg 1 mg 1 mg 1 mg 1 mg 1 mg 1 mg

Abstract

The invention relates to a solid administration form, protected from parenteral abuse and containing at least one viscosity-increasing agent in addition to one or more active substances that have parenteral abuse potential. The agent forms, when a necessary minimum amount of an aqueous liquid is added, on the basis of an extract obtained from the administration form, a preferably injectable gel that remains visually distinct when introduced into another quantity of an aqueous liquid.

Description

  • The present invention relates to a solid dosage form with reduced parenteral abuse containing, in addition to one or more active ingredients with potential for abuse, at least one viscosity-increasing agent in quantities such that, on extraction with the assistance of a necessary minimum quantity of aqueous liquid, a gel is formed which can still preferably pass through a needle, which gel, however, remains visually distinguishable even after being introduced into a further quantity of an aqueous liquid.
  • Many pharmaceutical active ingredients, in addition to having excellent activity in their appropriate application, also have potential for abuse, i.e. they can be used by an abuser to bring about effects other than those intended. Opiates, for example, which are highly active in combating severe to very severe pain, are frequently used by abusers to induce a state of narcosis or euphoria.
  • Dosage forms which contain active ingredients with potential for abuse, even when taken orally in an abusively large quantity, do not usually give rise to the result desired by the abuser, namely a rapid rush or “kick”, because blood levels of the active ingredients increase only slowly. In order nevertheless to achieve the desired effects and enable abuse, the corresponding dosage forms are comminuted, for example ground, by the abuser and the active ingredient is extracted from the powder obtained by comminution of the dosage form with the assistance of a preferably aqueous liquid, preferably the minimum quantity necessary, and the resultant solution, optionally after filtration through cotton wool or cellulose wadding, is administered parenterally, in particular intravenously. Due to this parenteral administration, only the smallest possible quantities of an aqueous liquid are used for extraction, in particular so as to obtain the smallest possible injection volume with active ingredient which results in the desired rapid rush or “kick”. In this manner, parenteral administration, in comparison with oral administration, tends to give rise to an accelerated rise in levels of the active ingredient providing the abuser with the desired result.
  • In order to prevent this form of abuse, it has been proposed in U.S. Pat. No. 4,070,494 to prevent the extraction of an active ingredient from a dosage form by the addition of a swellable agent. On addition of water, this agent swells and ensures that only a small quantity of active ingredient containing liquid is obtained which can be administered parenterally by the abuser. The majority of this dosage form which has swollen is cannot be administered.
  • A corresponding approach to the prevention of parenteral abuse also underlies the multilayer tablet disclosed in WO 95/20947 which contains the active ingredient with potential for abuse and one or more gel formers each in different layers.
  • According to this prior art teaching, the viscosity-increasing agents are added in quantities such that the corresponding gel cannot be administered with the assistance of conventional hypodermic needles.
  • The object of the present invention was to provide a dosage form with at least reduced potential for abuse for active ingredients having with such potential, which dosage form prevents any preferably still possible parenteral, in particular intravenous, abuse of the active ingredients.
  • This object has been achieved by the provision of the solid dosage form according to the invention with at least reduced potential for parenteral abuse, which dosage form, in addition to one or more active ingredients with potential for abuse, comprises at least one viscosity-increasing agent in a quantity such that a gel which may preferably still pass through a needle is formed in an extract obtained from the dosage form with the assistance of a necessary minimum quantity of an aqueous liquid, which gel remains visually distinguishable when introduced into a further quantity of an aqueous liquid.
  • For the purposes of the present invention, visually distinguishable means that the active ingredient-containing gel formed by extraction from the dosage form with the assistance of a necessary minimum quantity of aqueous liquid, when introduced with a hypodermic needle with a diameter of 0.9 mm 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 min.
  • The increase in viscosity of the gel with the assistance of the selected viscosity-increasing agent means that, although this has been rendered more difficult, the gel may still be passed through a needle or injected. It also means that when the resultant extract or gel is introduced at 37° C. into a further quantity of aqueous liquid, for example also by injection into blood, a largely cohesive thread is initially obtained which, while it may be broken up into smaller fragments by mechanical action, it cannot be dispersed or even dissolved in such a manner that it may safely be administered parenterally, in particular intravenously.
  • Intravenous administration of such an extract would most probably result in obstruction of blood vessels, associated with serious embolism or even death of the abuser.
  • For the purposes of the present invention, an extract or gel obtained from the dosage form according to the invention with the assistance of a necessary minimum quantity of an aqueous liquid, preferably water, is deemed to be passable through a needle if the gel formed in this manner can still be drawn up and injected back out of a hypodermic needle with a diameter of 2 mm, preferably of 1.5 mm, particularly preferably of 0.6 mm. Pharmaceutical active ingredients with potential for abuse are known to the person skilled in the art, as are the quantities 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 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 dosage form according to the invention is also suitable for the administration of a plurality of active ingredients. It is preferably used for the administration of a single active ingredient.
  • The dosage form according to the invention is in particular suitable for preventing abuse of a pharmaceutical active ingredient selected from the group consisting of opiates, opioids, tranquillisers, preferably benzodiazepines, stimulants and other narcotics.
  • The dosage form according to the invention is very particularly preferably suitable for preventing abuse of an opiate, opioid, tranquilliser or another narcotic, which is selected from the group consisting of N-{1-[2-(4-Ethyl-5-oxo-2-tetrazolin-1-yl)ethyl]-4-methoxymethyl-4-piperidyl}propionanilide (alfentanil), 5,5-diallylbarbituric acid (allobarbital), allylprodine, alphaprodine, 8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]-benzodiazepine (alprazolam), 2-diethylaminopropiophenone (amfepramone), (±)-a-methylphenethylamine (amphetamine), 2-(a-methylphenethylamino)-2-phenylacetonitrile (amphetaminil), 5-ethyl-5-isopentylbarbituric acid (amobarbital), anileridine, apocodeine, 5,5-diethylbarbituric acid (barbital), benzylmorphine, bezitramide, 7-bromo-5-(2-pyridyl)-1H-1,4-benzodiazepine-2(3H)-one (bromazepam), 2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine (brotizolam), 17-cyclopropylmethyl-4,5a-epoxy-7a[(S)-1-hydroxy-1,2,2-trimethyl-propyl]-6-methoxy-6,14-endo-ethanomorphinan-3-ol (buprenorphine), 5-butyl-5-ethylbarbituric acid (butobarbital), butorphanol, (7-chloro-1,3-dihydro-1-methyl-2-oxo-5-phenyl-2H-1,4-benzodiazepin-3-yl) dimethylcarbamate (camazepam), (1S,2S)-2-amino-1-phenyl-1-propanol (cathine/D-norpseudoephedrine), 7-chloro-N-methyl-5-phenyl-3H-1,4-benzodiazepin-2-ylamine 4-oxide (chlordiazepoxide), 7-chloro-1-methyl-5-phenyl-1H-1,5-benzodiazepine-2,4(3H,5H)-dione (clobazam), 5-(2-chlorophenyl)-7-nitro-1H-1,4-benzodiazepin-2(3H)-one (clonazepam), clonitazene, 7-chloro-2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-carboxylic acid (clorazepate), 5-(2-chlorophenyl)-7-ethyl-1-methyl-1H-thieno[2,3-e][1,4]diazepin-2(3H)-one (clotiazepam), 10-chloro-11b-(2-chlorophenyl)-2,3,7,11b-tetrahydrooxazolo[3,2-d][1,4]benzodiazepin-6(5H)-one (cloxazolam), (−)-methyl[3β-benzoyloxy-2β(1aH,5aH)-tropane carboxylate] (cocaine), 4,5a-epoxy-3-methoxy-17-methyl-7-morphinen-6a-ol (codeine), 5-(1-cyclohexenyl)-5-ethyl barbituric acid (cyclobarbital), cyclorphan, cyprenorphine, 7-chloro-5-(2-chlorophenyl)-1H-1,4-benzodiazepin-2(3H)-one (delorazepam), desomorphine, dextromoramide, (+)-(1-benzyl-3-dimethylamino-2-methyl-1-phenylpropyl)propionate (dextropropoxyphene), dezocine, diampromide, diamorphone, 7-chloro-1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one (diazepam), 4,5a-epoxy-3-methoxy-17-methyl-6a-morphinanol (dihydrocodeine), 4,5a-epoxy-17-methyl-3,6a-morphinandiol (dihydromorphine), dimenoxadol, dimephetamol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, (6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol (dronabinol), eptazocine, 8-chloro-6-phenyl-4H-[1,2,4]triazolo[4,3-(a)][1,4]benzodiazepine (estazolam), ethoheptazine, ethylmethylthiambutene, ethyl [7-chloro-5-(2-fluorophenyl)-2,3-dihydro-2-oxo-1H-1,4-benzodiazepine-3-carboxylate] (ethyl loflazepate), 4,5a-epoxy-3-ethoxy-17-methyl-7-morphinen-6a-ol (ethylmorphine), etonitazene, 4,5a-epoxy-7a-(1-hydroxy-1-methylbutyl)-6-methoxy-17-methyl-6,14-endo-etheno-morphinan-3-ol (etorphine), N-ethyl-3-phenyl-8,9,10-trinorbornan-2-ylamine (fencamfamine), 7-[2-(a-methylphenethylamino)ethyl]-theophylline) (fenethylline), 3-(a-methylphenethylamino)propionitrile (fenproporex), N-(1-phenethyl-4-piperidyl)propionanilide (fentanyl), 7-chloro-5-(2-fluorophenyl)-1-methyl-1H-1,4-benzodiazepin-2(3H)-one (fludiazepam), 5-(2-fluorophenyl)-1-methyl-7-nitro-1H-1,4-benzodiazepin-2(3H)-one (flunitrazepam), 7-chloro-1-(2-diethylaminoethyl)-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2(3H)-one (flurazepam), 7-chloro-5-phenyl-1-(2,2,2-trifluoroethyl)-1H-1,4-benzodiazepin-2(3H)-one (halazepam), 10-bromo-11b-(2-fluorophenyl)-2,3,7,11b-tetrahydro[1,3]oxazolyl[3,2-d][1,4]benzodiazepin-6(5H)-one (haloxazolam), heroin, 4,5a-epoxy-3-methoxy-17-methyl-6-morphinanone (hydrocodone), 4,5a-epoxy-3-hydroxy-17-methyl-6-morphinanone (hydromorphone), hydroxypethidine, isomethadone, hydroxymethylmorphinan, 11-chloro-8,12b-dihydro-2,8-dimethyl-12b-phenyl-4H-[1,3]oxazino[3,2-d][1,4]benzodiazepine-4,7(6H)-dione (ketazolam), 1-[4-(3-hydroxyphenyl)-1-methyl-4-piperidyl]-1-propanone (ketobemidone), (3S,6S)-6-dimethylamino-4,4-diphenylheptan-3-yl acetate (levacetylmethadol (LAAM)), (−)-6-dimethylamino-4,4-diphenol-3-heptanone (levomethadone), (−)-17-methyl-3-morphinanol (levorphanol), levophenacylmorphane, lofentanil, 6-(2-chlorophenyl)-2-(4-methyl-1-piperazinylmethylene)-8-nitro-2H-imidazo[1,2-a][1,4]-benzodiazepin-1(4H)-one (loprazolam), 7-chloro-5-(2-chlorophenyl)-3-hydroxy-1H-1,4-benzodiazepin-2(3H)-one (lorazepam), 7-chloro-5-(2-chlorophenyl)-3-hydroxy-1-methyl-1H-1,4-benzodiazepin-2(3H)-one (lormetazepam), 5-(4-chlorophenyl)-2,5-dihydro-3H-imidazo[2,1-a]isoindol-5-ol (mazindol), 7-chloro-2,3-dihydro-1-methyl-5-phenyl-1H-1,4-benzodiazepine (medazepam), N-(3-chloropropyl)-a-methylphenethylamine (mefenorex), meperidine, 2-methyl-2-propyltrimethylene dicarbamate (meprobamate), meptazinol, metazocine, methylmorphine, N,a-dimethylphenethylamine (metamphetamine), (±)-6-dimethylamino-4,4-diphenol-3-heptanone (methadone), 2-methyl-3-o-tolyl-4(3H)-quinazolinone (methaqualone), methyl[2-phenyl-2-(2-piperidyl)acetate] (methylphenidate), 5-ethyl-1-methyl-5-phenylbarbituric acid (methylphenobarbital), 3,3-diethyl-5-methyl-2,4-piperidinedione (methyprylon), metopon, 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine (midazolam), 2-(benzhydrylsulfinyl)acetamide (modafinil), 4,5a-epoxy-17-methyl-7-morphinen-3,6a-diol (morphine), myrophine, (±)-trans-3-(1,1-dimethylheptyl)-7,8,10,10a-tetrahydro-1-hydroxy-6,6-dimethyl-6H-dibenzo-[b,d]pyran-9(6aH)-one (nabilone), nalbuphene, nalorphine, narceine, nicomorphine, 1-methyl-7-nitro-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one (nimetazepam), 7-nitro-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one (nitrazepam), 7-chloro-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one (nordazepam), norlevorphanol, 6-dimethylamino-4,4-diphenyl-3-hexanone (normethadone), normorphine, norpipanone, the exudation from plants belonging to the species Papaver somniferum (opium), 7-chloro-3-hydroxy-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one (oxazepam), (cis-trans)-10-chloro-2,3,7,11b-tetrahydro-2-methyl-11b-phenyloxazolo[3,2-d][1,4]benzodiazepin-6-(5H)-one (oxazolam), 4,5a-epoxy-14-hydroxy-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, 2-imino-5-phenyl-4-oxazolidinone (pemoline), 1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(3-methyl-2-butenyl)-2,6-methano-3-benzazocin-8-ol (pentazocine), 5-ethyl-5-(1-methylbutyl)-barbituric acid (pentobarbital), ethyl-(1-methyl-4-phenyl-4-piperidinecarboxylate) (pethidine), phenadoxone, phenomorphane, phenazocine, phenoperidine, piminodine, pholcodeine, 3-methyl-2-phenylmorpholine (phenmetrazine), 5-ethyl-5-phenylbarbituric acid (phenobarbital), a,a-dimethylphenethylamine (phentermine), 7-chloro-5-phenyl-1-(2-propynyl)-1H-1,4-benzodiazepin-2(3H)-one (pinazepam), a-(2-piperidyl)benzhydryl alcohol (pipradrol), 1′-(3-cyano-3,3-diphenylpropyl)[1,4′-bipiperidine]-4′-carboxamide (piritramide), 7-chloro-1-(cyclopropylmethyl)-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one (prazepam), profadol, proheptazine, promedol, properidine, propoxyphene, N-(1-methyl-2-piperidinoethyl)-N-(2-pyridyl)propionamide, methyl {3-[4-methoxycarbonyl-4-(N-phenylpropanamido)piperidino]propanoate} (remifentanil), 5-sec-butyl-5-ethylbarbituric acid (secbutabarbital), 5-allyl-5-(1-methylbutyl)-barbituric acid (secobarbital), N-{4-methoxymethyl-1-[2-(2-thienyl)ethyl]-4-piperidyl}propionanilide (sufentanil), 7-chloro-2-hydroxy-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one (temazepam), 7-chloro-5-(1-cyclohexenyl)-1-methyl-1H-1,4-benzodiazepin-2(3H)-one (tetrazepam), ethyl (2-dimethylamino-1-phenyl-3-cyclohexene-1-carboxylate) (tilidine, cis and trans)), tramadol, 8-chloro-6-(2-chlorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine (triazolam), 5-(1-methylbutyl)-5-vinylbarbituric acid (vinylbital), (1R*,2R*)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol, (1R,2R,4S)-2-(dimethylamino)methyl-4-(p-fluorobenzyloxy)-1-(m-methoxyphenyl)cyclohexanol and for corresponding stereoisomeric compounds, the corresponding derivatives thereof in each case, in particular esters or ethers, and the physiologically acceptable compounds thereof in each case, in particular the salts and solvates thereof.
  • The compounds (1R*,2R*)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol and (1R,2R,4S)-2-(dimethylamino)methyl-4-(p-fluorobenzyloxy)-1-(m-methoxyphenyl)cyclohexanol, the physiologically acceptable compounds thereof, in particular the hydrochlorides thereof and processes for the production thereof are respectively known, for example, from EP-A-693475 and EP-A-780369. The corresponding descriptions are hereby introduced as a reference and are deemed to be part of the disclosure.
  • In order to verify whether a viscosity-increasing agent is suitable for use in the dosage form according to the invention, said agent is first formulated in a corresponding dosage form in quantities such that there is no appreciable (±5%) influence on active ingredient release relative to a dosage form without viscosity-increasing agent. The corresponding dosage form is moreover comminuted, preferably ground, and extracted with 10 ml water at 25° C. If a gel is furthermore formed which meets the above-stated conditions, the corresponding viscosity-increasing agent is suitable for the production of a dosage form according to the invention.
  • Preferably, one or more viscosity-increasing agents are used in the dosage form according to the invention, said agents being selected from the group consisting of microcrystalline cellulose with 11 wt. % carboxymethylcellulose sodium (Avicel® RC 591), carboxymethylcellulose sodium (Blanose®, CMC-Na C3001P®, 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 2611-75®), iota-carrageenan (Frimulsion D021®), karaya gum, gellan gum (Kelcogel F®, Kelcogel LT100®), galactomannan (Meyprogat 150®), tara stone flour (Polygum 4311®), 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®). The names stated in brackets are the trade names by which the materials are known commercially.
  • In general, a quantity of 0.1 to 25 wt. %, preferably of 0.5 to 15 wt. %, particularly preferably of 1-10 wt. % of the viscosity-increasing agent, relative to the total formulation, is sufficient in order to meet the above-stated conditions. The viscosity-increasing agents are preferably present in the dosage form according to the invention in quantities of =5 mg, particularly preferably of =10 mg per dosage form, i.e. per administration unit.
  • In a particularly preferred embodiment of the present invention, the viscosity-increasing agents used are those which, in addition to the above-stated conditions, also form a gel which encloses air bubbles on extraction from the dosage form with the necessary minimum quantity of aqueous liquid. 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 active ingredient or ingredients with potential for abuse and the viscosity-increasing agents and optionally physiologically acceptable auxiliary substances may be formulated to yield the dosage form according to the invention in accordance with conventional methods known to the person skilled in the art. Corresponding methods for formulating the dosage form according to the invention are known per se 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.
  • Surprisingly, due to the inventive selection of the viscosity-increasing agents, it is possible to combine the active ingredients and the viscosity-increasing agents in the dosage form according to the invention without spatial separation from one another, without there being any impairment of release of the active ingredient from the correctly administered dosage form relative to a corresponding dosage form which does not comprise the viscosity-increasing agent.
  • Obviously, however, it is also possible to combine the viscosity-increasing agents and the active ingredients in the dosage form in a mutually spatially separated arrangement.
  • The parenteral abuse-proofed solid dosage forms according to the invention are preferably suitable for oral or rectal administration, particularly preferably for oral administration.
  • Where the dosage form according to the invention is intended for rectal administration, it preferably assumes the form of a suppository.
  • If the dosage form according to the invention is intended for oral administration, it preferably assumes the form of a tablet, a capsule or of an oral osmotic therapeutic system (OROS).
  • Oral osmotic therapeutic systems and suitable materials and processes for the production thereof are known per se to the person skilled in the art, for example 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.
  • The corresponding oral osmotic therapeutic system may preferably assume the form of a single or twin chamber system, in each case with a single layer or multilayer structure. In these systems, the push layer, i.e. the layer which produces the osmotic pressure by swelling, by means of which the overlying layer is expelled from the system, preferably at least in part consists of the viscosity-increasing agents used according to the invention.
  • In a further preferred embodiment of the present invention, the orally administrable dosage form according to the invention assumes multiparticulate form containing in each case the complete mixture of active ingredient and viscosity-increasing agent, preferably in the form of microtablets, microcapsules, micropellets, granules, spheroids, beads or pellets, preferably packaged in capsules or press-moulded into tablets. The multiparticulate forms preferably have a size in the range from 0.1 to 3 mm, particularly preferably in the range from 0.5 to 2 mm.
  • The dosage form according to the invention may preferably also comprise one or more active ingredients, blended with the viscosity-increasing agent, at least in part in delayed-release form, wherein delayed release may be achieved with the assistance of conventional materials and processes known to the person skilled in the art, for example by embedding the active ingredient in a delayed-release matrix or by applying one or more delayed-release coatings.
  • Delayed release of the active ingredient may preferably also be achieved by purposeful selection of one or more of the above-stated viscosity-increasing agents in suitable quantities as the matrix material. The person skilled in the art may determine the agents and the quantity thereof suitable for the particular desired release by simple preliminary testing, wherein it must, of course, be ensured that, as described above, gel formation occurs when the attempt is made to abuse the resultant dosage form.
  • In any event, it must be ensured that the delayed-release auxiliary substances, and likewise further optionally present auxiliary substances, do not interfere with gel formation or impair the stability of the gel which is formed.
  • If the dosage form according to the invention is intended for oral administration, it may also comprise a coating which is resistant to gastric juices and dissolves as a function of the pH value of the release environment.
  • By means of this coating, it is possible to ensure that, when correctly administered, the dosage form according to the invention passes through the stomach undissolved and the active ingredient is only released in the intestines. The coating which is resistant to gastric juices preferably dissolves at a pH value of between 5 and 7.5.
  • Corresponding materials and methods for the controlled release of active ingredients 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.
  • In a further preferred embodiment, the dosage form according to the invention contains the active ingredient not only in its delayed-release form, but also in its non-delayed-release form. By combination with the immediately released active ingredient, it is possible to obtain an initial dose for rapid pain relief. The slow release from the delayed-release form then prevents any rapid decline in action.
  • 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.
    • EXAMPLES Example 1 Matrix Tablets with the Following Composition Per Tablet
  • (−)-(1R,2R)-3-(3-Dimethylamino-1-ethyl-2-methyl- 100 mg
    propyl)phenol hydrochloride
    Hydroxypropylmethylcellulose (Metolose 90 SH 70 mg
    100,000 from Shinetsu), 100,000 mPa · s
    Xanthan, NF 10 mg
    Microcrystalline cellulose (Avicel PH 102 from FMC) 123 mg
    Highly disperse silicon dioxide 4 mg
    Magnesium stearate 3 mg
    Total quantity 310 mg
  • were produced in the following manner in a batch size of 1000 tablets: All the constituents were weighed out and screened in Quadro Comil U10 screening machine using a screen size of 0.813 mm, mixed in a container mixer (Bohle LM 40) for 15 min±15 s at a rotational speed of 20±1 rpm and pressed on a Korsch EKO eccentric press to form biconvex tablets with a diameter of 10 mm, a radius of curvature of 8 mm and an average tablet weight of 310 mg.
  • In vitro release was determined using the Ph. Eur. paddle method at 75 rpm in 900 ml of pH 6.8 buffer to Ph. Eur. at 37° C., with detection by UV spectrometry, and is shown in the following Table, together with a comparison with a corresponding tablet with 80 mg of hydroxypropylmethylcellulose (“HPMC”) without addition of xanthan.
  • Total quantity of active Total quantity of active
    ingredient released [%] from ingredient released [%] from
    Time tablets according to Example 1 tablets with 80 mg HPMC
    [min] (70 mg HPMC + 10 mg xanthan) (without xanthan)
    0 0 0
    30 19 18
    240 62 59
    480 83 80
    600 88 87
    720 93 93
  • One of the tablets containing xanthan was ground and shaken with 10 ml of water. A viscous, turbid suspension formed. Once the coarse, solid components of the suspension had settled out, the gel which had formed was drawn up into a syringe with a 0.9 mm diameter needle. The drawn up gel was injected into water at 37° C. and threads, which did not mix with the water, with the diameter of the needle remained clearly discernible. While the threads could be broken up by stirring, they could not be dissolved and the thread fragments remained visible to the naked eye. Were such an extract to be injected into blood vessels, vessel blockages would occur.
    • Example 2 Comparative Example Regarding Very Poor Needle Passage Properties
  • Matrix tablets with the following composition per tablet
  •
    (−)-(1R,2R)-3-(3-Dimethylamino-1-ethyl-2-methyl- 100 mg
    propyl)phenol hydrochloride
    Hydroxypropylmethylcellulose (Metolose 90 SH 40 mg
    100,000 from Shinetsu), 100,000 mPa · s
    Xanthan, NF 40 mg 12%?
    Microcrystalline cellulose (Avicel PH 102 from FMC) 123 mg
    Highly disperse silicon dioxide 4 mg
    Magnesium stearate 3 mg
    Total quantity 310 mg

    were produced as stated in Example 1 and their release characteristics were investigated.
  • Total quantity of
    active ingredient
    Time [min] released [%]
    0 0
    30 19
    240 61
    480 81
    600 87
    720 91
  • One of the tablets was ground and shaken with 10 ml of water. A viscous, turbid suspension with enclosed air bubbles formed, the viscosity of which was greater than in Example 1. Once the coarse, solid components of the suspension had settled out, the gel which had formed was drawn up into a syringe with a 0.9 mm diameter needle. The drawn up gel was injected into water at 37° C. and threads, which did not mix with the water, with the diameter of the needle were clearly discernible. While the threads could be broken up by stirring, they could not be dissolved and the thread fragments remained visible to the naked eye. Were such a gel to be injected into blood vessels, vessel blockages would occur.
    • Example 3 Matrix Tablets with the Following Composition Per Tablet
  • (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl- 100 mg
    propyl)phenol hydrochloride
    Xanthan, NF 80 mg
    Microcrystalline cellulose (Avicel PH 102 from FMC) 123 mg
    Highly disperse silicon dioxide 4 mg
    Magnesium stearate 3 mg
    Total quantity 310 mg

    were produced as stated in Example 1.
  • One of these tablets was ground and shaken with 10 ml of water. A viscous, turbid suspension, which had enclosed air bubbles, formed, the viscosity of which was higher than in Example 1. Once the coarse, solid components of the suspension had settled out, the gel which had formed was drawn up into a syringe with a 0.9 mm diameter needle. The drawn up gel was injected into water at 37° C. and clearly discernible threads, which did not mix with the water, with the diameter of the needle were visible. While the threads could be broken up by stirring, they could not be dissolved and the thread fragments remained visible to the naked eye. Were such a gel to be injected into blood vessels, vessel blockages would occur.
    • Examples 4-7 Matrix Tablets with the Following Composition Per Tablet
  • Example 4 5 6 7
    (−)-(1R,2R)-3-(3-Dimethylamino-1-ethyl-2-methyl- 100 mg 100 mg 100 mg 100 mg
    propyl)phenol hydrochloride
    Hydroxypropylmethylcellulose (Metolose 90 SH 80 mg 80 mg 80 mg 80 mg
    100,000 from Shinetsu), 100,000 mPa · s
    Carboxymethylcellulose (Tylose C300) 10 mg
    Carboxymethylcellulose (Tylose C600) 10 mg
    Hydroxyethylcellulose (Tylose H300) 10 mg
    Hydroxyethylcellulose (Tylose H4000) 10 mg
    Microcrystalline cellulose (Avicel PH 102 from FMC) 123 mg 123 mg 123 mg 123 mg
    Highly disperse silicon dioxide 4 mg 4 mg 4 mg 4 mg
    Magnesium stearate 3 mg 3 mg 3 mg 3 mg
    Total quantity 320 mg 320 mg 320 mg 320 mg

    were produced as stated in Example 1.
  • One of each of these tablets was ground and shaken with 10 ml of water. A viscous, turbid suspension with enclosed air bubbles formed. Once the coarse, solid components of the suspension had settled out, the [gel] was drawn up into a syringe with a 0.9 mm diameter needle. The drawn up gel was injected into water at 37° C. and clearly visible threads, which did not mix with the water, with the diameter of the needle remained discernible. While the threads could be broken up by stirring, they could not be dissolved and the thread fragments remained visible to the naked eye. Were such a gel to be injected into blood vessels, vessel blockages would occur.
    • Examples 8-13 Matrix Tablets with the Following Composition Per Tablet
  • Example
    8 9 10 11 12 13
    Morphine sulfate 60 mg 60 mg 60 mg 60 mg 60 mg 60 mg
    pentahydrate
    Hydroxypropylmethylcellulose 60 mg 60 mg 60 mg 60 mg 60 mg 60 mg
    (Metolose 90 SH 15,000 from
    Shinetsu), 15,000 mPa·s
    Xanthan, NF 10 mg 30 mg
    Carboxymethylcellulose 10 mg
    (Tylose C300)
    Carboxymethylcellulose 10 mg
    (Tylose C600)
    Hydroxyethylcellulose (Tylose 10 mg
    H300)
    Hydroxyethylcellulose (Tylose 10 mg
    H4000)
    Microcrystalline cellulose 123 mg  123 mg  123 mg  123 mg  123 mg  123 mg 
    (Avicel PH 102 from FMC)
    Highly disperse silicon dioxide  4 mg  4 mg  4 mg  4 mg  4 mg  4 mg
    Magnesium stearate  3 mg  3 mg  3 mg  3 mg  3 mg  3 mg
  • One of each of these tablets was ground and shaken with 10 ml of water. A viscous, turbid suspension with enclosed air bubbles formed. Once the coarse, solid components of the suspension had settled out, the [gel] was drawn up into a syringe with a 0.9 mm diameter needle. The drawn up gel was injected into water at 37° C. and clearly visible threads, which did not mix with the water, with the diameter of the needle remained discernible. While the threads could be broken up by stirring, they could not be dissolved and the thread fragments remained visible to the naked eye. Were such a gel to be injected into blood vessels, vessel blockages would occur.
    • Examples 14-18 Capsules with the Following Composition of the Simple Powder Mixture Per Capsule Size 4 Capsule
  • Example
    14 15 16 17 18
    Morphine sulfate pentahydrate 20 mg 20 mg 20 mg 20 mg 20 mg
    Xanthan, NF 10 mg
    Carboxymethylcellulose (Tylose C300) 10 mg
    Carboxymethylcellulose (Tylose C600) 10 mg
    Hydroxyethylcellulose (Tylose H300) 10 mg
    Hydroxyethylcellulose (Tylose H4000) 10 mg
    Microcrystalline cellulose (Avicel PH 102 68 mg 68 mg 68 mg 68 mg 68 mg
    from FMC)
    Highly disperse silicon dioxide  1 mg  1 mg  1 mg  1 mg  1 mg
    Magnesium stearate  1 mg  1 mg  1 mg  1 mg  1 mg
  • One of each of these tablets was ground and shaken with 10 ml of water. A viscous, turbid suspension with enclosed air bubbles formed. Once the coarse, solid components of the suspension had settled out, the [gel] was drawn up into a syringe with a 0.9 mm diameter needle. The drawn up gel was injected into water at 37° C. and clearly visible threads, which did not mix with the water, with the diameter of the needle remained discernible. While the threads could be broken up by stirring, they could not be dissolved and the thread fragments remained visible to the naked eye. Were such a gel to be injected into blood vessels, vessel blockages would occur.

Claims (15)

1-12. (canceled)
13. A solid dosage form for oral administration, comprising, in addition to one or more active ingredients with potential for abuse selected from the group consisting of opiates, opioids, tranquillizers, stimulants and narcotics, at least one viscosity-increasing agent in a quantity equal to or greater than 5 mg per dosage form and such that an aqueous extract obtained from the dosage form with 10 ml of water at 25° C. forms a gel which can still pass through a needle having a diameter of 0.9 mm and remains visually distinguishable when introduced by a needle into a further quantity of an aqueous liquid.
14. A dosage form according to claim 13, wherein the active ingredient is an opiate, opioid, tranquillizer or a narcotic selected from the group consisting of N-{1-[2-(4-Ethyl-5-oxo-2-tetrazolin-1-yl)ethyl]-4-methoxymethyl-4-piperidyl}propionanilide (alfentanil), 5,5-diallylbarbituric acid (allobarbital), allylprodine, alphaprodine, 8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]-benzodiazepine (alprazolam), 2-diethylaminopropiophenone (amfepramone), (.+−.)-α-methylphenethylamine (amphetamine), 2-(-α-methylphenethylamino)-2-phenylacetonitrile (amphetaminil), 5-ethyl-5-isopentylbarbituric acid (amobarbital), anileridine, apocodeine, 5,5-diethylbarbituric acid (barbital), benzylmorphine, bezitramide, 7-bromo-5-(2-pyridyl)-1H-1,4-benzodiazepine-2(3H)-one (bromazepam), 2-bromo-4-(2-chlorophenyl)-9-methyl-1-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine (brotizolam), 17-cyclopropylmethyl-4,5a-epoxy-7a[(S)-1-hydroxy-1,2,2-trimethyl-propyl]-6-methoxy-6,14-endo-ethanomorphinan-3-ol (buprenorphine), 5-butyl-5-ethylbarbituric acid (butobarbital), butorphanol, (7-chloro-1,3-dihydro-1-methyl-2-oxo-5-phenyl-2H-1,4-benzodiazepin-3-yl)dimethylcarbamate (camazepam), (1S,2S)-2-amino-1-phenyl-1-propanol (cathine/D-norpseudoephedrine), 7-chloro-N-methyl-5-phenyl-3H-1,4-benzodiazepin-2-yl amine 4-oxide (chlordiazepoxide), 7-chloro-1-methyl-5-phenyl-1H-1,5-benzodiazepine-2,4(3H,5H)-dione (clobazam), 5-(2-chlorophenyl)-7-nitro-1H-1,4-benzodiazepin-2(3H)-one (clonazepam), clonitazene, 7-chloro-2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-carboxylic acid (clorazepate), 5-(2-chlorophenyl)-7-ethyl-1-methyl-1H-thieno[2,3-e][1,4]diazepin-2(3H)-one (clotiazepam), 10-chloro-11b-(2-chlorophenyl)-2,3,7,11b-tetrahydrooxazolo[3,2-d][1,4]benzodiazepin-6(5H)-one (cloxazolam), (−)-methyl-[3.β.-benzoyloxy-2.β.(1.-α-.H,5.-α-.H)-tropane carboxylate] (cocaine), 4,5.α.-epoxy-3-methoxy-17-methyl-7-morphinen-6-.alpha.-ol (codeine), 5-(1-cyclohexenyl)-5-ethyl barbituric acid (cyclobarbital), cyclorphan, cyprenorphine, 7-chloro-5-(2-chlorophenyl)-1H-1,4-benzodiazepin-2(3H)-one (delorazepam), desomorphine, dextromoramide, (+)-(1-benzyl-3-dimethylamino-2-methyl-1-phenylpropyl)propionate (dextropropoxyphene), dezocine, diampromide, diamorphone, 7-chloro-1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one (diazepam), 4,5.alpha.-epoxy-3-methoxy-17-methyl-6.alpha.-morphinanol (dihydrocodeine), 4,5.alpha.-epoxy-17-methyl-3,6a-morphinandiol (dihydromorphine), dimenoxadol, dimephetamol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, (6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol (dronabinol), eptazocine, 8-chloro-6-phenyl-4H-[1,2,4]-triazolo[4,3-(a)][1,4]benzodiazepine (estazolam), ethoheptazine, ethylmethylthiambutene, ethyl[7-chloro-5-(2-fluorophenyl)-2,3-dihydro-2-oxo-1H-1,4-benzodiazepine-3-carboxylate](ethyl loflazepate), 4,5.α.-epoxy-3-ethoxy-17-methyl-7-morphinen-6.α.-ol (ethylmorphine-), etonitazene, 4,5.α.-epoxy-7.α.-(1-hydroxy-1-methylbutyl)-6-methoxy-17-methyl-6,14-endo-etheno-morphinan-3-ol (etorphine), N-ethyl-3-phenyl-8,9,10-trinorbornan-2-ylamine (fencamfamine), 7-[2-(.α.-methylphenethylamino)ethyl]-theophylline)(fenethylline), 3-(.α.-methylphenethylamino)propionitrile (fenproporex), N-(1-phenethyl-4-piperidyl)propionanilide (fentanyl), 7-chloro-5-(2-fluorophenyl)-1-methyl-1H-1,4-benzodiazepin-2(3H)-one (fludiazepam), 5-(2-fluorophenyl)-1-methyl-7-nitro-1H-1,4-benzodiazepin-2-(3H)-one (flunitrazepam), 7-chloro-1-(2-diethylaminoethyl)-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2(3H)-one (flurazepam), 7-chloro-5-phenyl-1-(2,2,2-trifluoroethyl)-1H-1,4-benzodiazepin-2(3H)-one (halazepam), 10-bromo-11b-(2-fluorophenyl)-2,3,7,11b-tetrahydro[1,3]oxazolyl[3,2-d][1,4]benzodiazepin-6(5H)-one (haloxazolam), heroin, 4,5.α.-epoxy-3-methoxy-17-methyl-6-morphinanone (hydrocodone), 4,5.α.-epoxy-3-hydroxy-17-methyl-6-morphinanone (hydromorphone), hydroxypethidine, isomethadone, hydroxymethylmorphinan, 11-chloro-8,12b-dihydro-2,8-dimethyl-12b-phenyl-4-H-[1,3]oxazino[3,2-d][1,4]benzodiazepine-4,7(6H)-dione (ketazolam), 1-[4-(3-hydroxyphenyl)-1-methyl-4-piperidyl]-1-propanone (ketobemidone), (3S,6S)-6-dimethylamino-4,4-diphenylheptan-3-yl acetate (levacetylmethadol (LAAM)), (−)-6-dimethylamino-4,4-diphenol-3-heptanone (levomethadone), (+17-methyl-3-morphinanol (levorphanol), levophenacylmorphane, lofentanil, 6-(2-chlorophenyl)-2-(4-methyl-1-piperazinylmethylene)-8-nitro-2H-imidazo[1,2-a][1,4]-benzodiazepin-1(4H)-one (loprazolam), 7-chloro-5-(2-chlorophenyl)-3-hydroxy-1H-1,4-benzodiazepin-2(3H)-one (lorazepam), 7-chloro-5-(2-chlorophenyl)-3-hydroxy-1-methyl-1H-1,4-benzodiazepin-2(3H)-one (lormetazepam), 5-(4-chlorophenyl)-2,5-dihydro-3H-imidazo[2,1-a]isoindol-5-ol (mazindol), 7-chloro-2,3-dihydro-1-methyl-5-phenyl-1H-1,4-benzodiazepine (medazepam), N-(3-chloropropyl)-.α.-methylphenethylamine (mefenorex), meperidine, 2-methyl-2-propyltrimethylene dicarbamate (meprobamate), meptazinol, metazocine, methylmorphine, N,.α.-dimethylphenethylamine (metamphetamine), (.+−.)-6-dimethylamino-4,4-diphenol-3-heptanone (methadone), 2-methyl-3-o-tolyl-4(3H)-quinazolinone (methaqualone), methyl[2-phenyl-2-(2-piperidyl)acetate](methylphenidate), 5-ethyl-1-methyl-5-phenylbarbituric acid (methylphenobarbital), 3,3-diethyl-5-methyl-2,4-piperidinedione (methyprylon), metopon, 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine-(midazolam), 2-(benzhydrylsulfinyl)acetamide (modafinil), 4,5.α.-epoxy-17-methyl-7-morphinen-3,6.α.-diol (morphine), myrophine, (.+−.)-trans-3-(1,1-dimethylheptyl)-7,8,10,10.α.-tetrahydro-1-hydroxy-6,6-dimethyl-6H-dibenzo-[b,d]pyran-9(6.α.H)-one (nabilone), nalbuphene, nalorphine, narceine, nicomorphine, 1-methyl-7-nitro-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one (nimetazepam), 7-nitro-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one (nitrazepam), 7-chloro-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one (nordazepam), norlevorphanol, 6-dimethylamino-4,4-diphenyl-3-hexanone (normethadone), normorphine, norpipanone, the exudation from plants belonging to the species Papaver somniferum (opium), 7-chloro-3-hydroxy-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one (oxazepam), (cis-trans)-10-chloro-2,3,7,11b-tetrahydro-2-methyl-11b-phenyloxazolo[3,2-d][1,4]benzodiazepin-6-(5H)-one (oxazolam), 4,5.α.-epoxy-14-hydroxy-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), papavereturn, 2-imino-5-phenyl-4-oxazolidinone (pernoline), 1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(3-methyl-2-butenyl)-2,6-methano-3-benzazocin-8-ol (pentazocine), 5-ethyl-5-(1-methylbutyl)-barbituric acid (pentobarbital), ethyl-(1-methyl-4-phenyl-4-piperidinecarboxylate)(pethidine), phenadoxone, phenomorphane, phenazocine, phenoperidine, piminodine, pholcodeine, 3-methyl-2-phenylmorpholine (phenmetrazine), 5-ethyl-5-phenylbarbituric acid (phenobarbital), .α.,.α.-dimethylphenethylamine (phentermine), 7-chloro-5-phenyl-1-(2-propynyl)-1H-1,4-benzodiazepin-2(3H)-one (pinazepam), .α.-(2-piperidyl)benzhydryl alcohol (pipradrol), 1′-(3-cyano-3,3-diphenylpropyl)[1,4′-bipiperidine]-4′-carboxamide (piritramide), 7-chloro-1-(cyclopropylmethyl)-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one (prazepam), profadol, proheptazine, promedol, properidine, propoxyphene, N-(1-methyl-2-piperidinoethyl)-N-(2-pyridyl)propionamide, methyl {3-[4-methoxycarbonyl-4-(N-phenylpropanamido)piperidino]propanoate}(remifentanil), 5-sec-butyl-5-ethylbarbituric acid (secbutabarbital), 5-allyl-5-(1-methylbutyl)-barbituric acid (secobarbital), N-{4-methoxymethyl-1-[2-(2-thienyl)ethyl]-4-piperidyl}propionanilide (sufentanil), 7-chloro-2-hydroxy-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one (temazepam), 7-chloro-5-(1-cyclohexenyl)-1-methyl-1H-1,4-benzodiazepin-2(3H)-one (tetrazepam), ethyl (2-dimethylamino-1-phenyl-3-cyclohexene-1-carboxylate)(tilidine (cis and trans)), tramadol, 8-chloro-6-(2-chlorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine (triazolam), 5-(1-methylbutyl)-5-vinylbarbituric acid (vinylbital), (1R*,2R*)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol, (1R,2R,4S)-2-(dimethylamino)methyl-4-(p-fluorobenzyloxy)-1-(m-methoxyphenyl)cyclohexanol and corresponding stereoisomeric compounds in each case and corresponding stereoisomeric compounds, derivatives, esters or ethers and salts and solvates thereof.
15. A dosage form according to claim 14, wherein the active ingredient is an opioid selected from the group consisting of codeine, dihydrocodeine, dihydromorphine, fentanyl, hydrocodone, hydromorphone, morphine, opium, oxycodone, oxymorphone, and tramadol.
16. A dosage form according to claim 15, wherein the active ingredient is oxycodone.
17. A dosage form according to claim 13, comprising a stimulant selected from the group consisting of amphetamine, norpseudoephedrine, methylphenidate and bases, salts and solvates thereof.
18. A dosage form according to claim 13, comprising one or more viscosity-increasing agents selected from the group consisting of microcrystalline cellulose with 11 wt. % carboxymethylcellulose sodium, carboxymethylcellulose sodium, polyacrylic acid, locust bean flour, citrus pectin, waxy maize starch, sodium alginate, guar flour, iota-carrageenan, karaya gum, gellan gum, galactomannan, tara stone flour, propylene glycol alginate, apple pectin, lemon peel pectin, sodium hyaluronate, tragacanth, tara gum, fermented polysaccharide welan gum and xanthan gum.
19. A dosage form according to claim 13, in particulate form.
20. A dosage form according to claim 13, comprising at least one active ingredient in controlled release form.
21. A dosage form according to claim 13, comprising a coating resistant to gastric juices.
22. The dosage form of claim 13, wherein said tranquilizer is a benzodiazepine.
23. A dosage form according to claim 13, comprising the at least one viscosity-increasing agent in a quantity of >5 mg per administration unit.
24. A dosage form according to claim 13, in multiparticulate form.
25. A dosage form according to claim 15, wherein said multiparticulate form is in the form of microtablets, microcapsules, micropellets, granules, spheroids, beads or pellets.
26. A dosage form according to claim 16, packaged in capsules or press-moulded into tablets.
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US13/572,926 US20120308654A1 (en) 2002-06-17 2012-08-13 Abuse-proofed dosage form
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US14/069,439 US20140093559A1 (en) 2002-06-17 2013-11-01 Abuse-proofed dosage form
US14/527,911 US20150056147A1 (en) 2002-06-17 2014-10-30 Abuse-proofed dosage form
US15/245,424 US9675610B2 (en) 2002-06-17 2016-08-24 Abuse-proofed dosage form
US15/587,501 US20170239185A1 (en) 2002-06-17 2017-05-05 Abuse-proofed dosage form
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Cited By (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090004267A1 (en) * 2007-03-07 2009-01-01 Gruenenthal Gmbh Dosage Form with Impeded Abuse
US20090052818A1 (en) * 2007-07-10 2009-02-26 Jason Matthew Mitmesser Hybrid bearing
US8075872B2 (en) 2003-08-06 2011-12-13 Gruenenthal Gmbh Abuse-proofed dosage form
US8114383B2 (en) 2003-08-06 2012-02-14 Gruenenthal Gmbh Abuse-proofed dosage form
US8114384B2 (en) 2004-07-01 2012-02-14 Gruenenthal Gmbh Process for the production of an abuse-proofed solid dosage form
US8192722B2 (en) 2003-08-06 2012-06-05 Grunenthal Gmbh Abuse-proof dosage form
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
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
US8383152B2 (en) 2008-01-25 2013-02-26 Gruenenthal Gmbh Pharmaceutical dosage form
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
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
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
US9198861B2 (en) 2009-12-22 2015-12-01 Mallinckrodt Llc Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans
US9301918B2 (en) 2013-03-15 2016-04-05 Mallinckrodt Llc Abuse deterrent solid dosage form for immediate release with functional score
US9579285B2 (en) 2010-02-03 2017-02-28 Gruenenthal Gmbh Preparation of a powdery pharmaceutical composition by means of an extruder
US9636303B2 (en) 2010-09-02 2017-05-02 Gruenenthal Gmbh Tamper resistant dosage form comprising an anionic polymer
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
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
US9925146B2 (en) 2009-07-22 2018-03-27 Grünenthal GmbH Oxidation-stabilized tamper-resistant dosage form
US9993422B2 (en) 2012-04-18 2018-06-12 SpecGx LLC Immediate release, abuse deterrent pharmaceutical compositions
US10058548B2 (en) 2003-08-06 2018-08-28 Grünenthal GmbH Abuse-proofed dosage form
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
US10624862B2 (en) 2013-07-12 2020-04-21 Grünenthal GmbH Tamper-resistant dosage form containing ethylene-vinyl acetate polymer
US10695297B2 (en) 2011-07-29 2020-06-30 Grünenthal GmbH Tamper-resistant tablet providing immediate drug release
US10729658B2 (en) 2005-02-04 2020-08-04 Grünenthal GmbH Process for the production of an abuse-proofed dosage form
US10744097B2 (en) 2013-03-15 2020-08-18 R.P. Scherer Technologies, Llc Abuse resistant capsule
US10842750B2 (en) 2015-09-10 2020-11-24 Grünenthal GmbH Protecting oral overdose with abuse deterrent immediate release formulations
US11224576B2 (en) 2003-12-24 2022-01-18 Grünenthal GmbH Process for the production of an abuse-proofed dosage form
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
US11844865B2 (en) 2004-07-01 2023-12-19 Grünenthal GmbH Abuse-proofed oral dosage form

Families Citing this family (63)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HU230828B1 (en) 1999-10-29 2018-08-28 Euro Celtique Sa Controlled release hydrocodone formulations
US10179130B2 (en) 1999-10-29 2019-01-15 Purdue Pharma L.P. Controlled release hydrocodone formulations
WO2002036099A1 (en) 2000-10-30 2002-05-10 Euro-Celtique S.A. Controlled release hydrocodone formulations
US20030068375A1 (en) 2001-08-06 2003-04-10 Curtis Wright Pharmaceutical formulation containing gelling agent
EP1610767B1 (en) 2003-03-26 2011-01-19 Egalet A/S Morphine controlled release system
US7201920B2 (en) 2003-11-26 2007-04-10 Acura Pharmaceuticals, Inc. Methods and compositions for deterring abuse of opioid containing dosage forms
PT1765292T (en) 2004-06-12 2017-12-29 Collegium Pharmaceutical Inc Abuse-deterrent drug formulations
DE102004032103A1 (en) * 2004-07-01 2006-01-19 Grünenthal GmbH Anti-abuse, oral dosage form
DE102004045037A1 (en) * 2004-09-15 2006-03-16 Basf Ag Pharmaceutical dosage forms with difficult extractability of a sympathomimetic from the dosage form
US20080152595A1 (en) * 2004-11-24 2008-06-26 Acura Pharmaceuticals, Inc. Methods and compositions for deterring abuse of orally administered pharmaceutical products
US20090082466A1 (en) * 2006-01-27 2009-03-26 Najib Babul Abuse Resistant and Extended Release Formulations and Method of Use Thereof
WO2008134071A1 (en) * 2007-04-26 2008-11-06 Theraquest Biosciences, Inc. Multimodal abuse resistant extended release formulations
US8329744B2 (en) * 2005-11-02 2012-12-11 Relmada Therapeutics, Inc. Methods of preventing the serotonin syndrome and compositions for use thereof
GB0606124D0 (en) * 2006-03-28 2006-05-03 Reckitt Benckiser Healthcare Buprenorphine derivatives and uses thereof
US20080069891A1 (en) 2006-09-15 2008-03-20 Cima Labs, Inc. Abuse resistant drug formulation
AU2007275034A1 (en) * 2006-07-21 2008-01-24 Lab International Srl Hydrophilic abuse deterrent delivery system
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
CA2687192C (en) 2007-06-04 2015-11-24 Egalet A/S Controlled release pharmaceutical compositions for prolonged effect
US8273798B2 (en) * 2007-06-04 2012-09-25 Shear Kershman Laboratories Tamper resistant lipid-based oral dosage form for opioid agonists
BRPI0821732A2 (en) 2007-12-17 2015-06-16 Labopharm Inc Controlled release formulations, solid dosage form, and use of controlled release formulation
US9226907B2 (en) 2008-02-01 2016-01-05 Abbvie Inc. Extended release hydrocodone acetaminophen and related methods and uses thereof
AU2009327312A1 (en) 2008-12-16 2011-08-04 Labopharm Europe Limited Misuse preventative, controlled release formulation
WO2010089132A1 (en) 2009-02-06 2010-08-12 Egalet A/S Immediate release composition resistant to abuse by intake of alcohol
EP2445487A2 (en) 2009-06-24 2012-05-02 Egalet Ltd. Controlled release formulations
CA2775890C (en) 2009-09-30 2016-06-21 Acura Pharmaceuticals, Inc. Methods and compositions for deterring abuse
US10668060B2 (en) 2009-12-10 2020-06-02 Collegium Pharmaceutical, Inc. Tamper-resistant pharmaceutical compositions of opioids and other drugs
CA2798702A1 (en) 2010-05-11 2011-11-17 Cima Labs Inc. Alcoholresistant metoprolol-containing extended-release oral dosage forms
SG191288A1 (en) 2010-12-22 2013-07-31 Purdue Pharma Lp Encased tamper resistant controlled release dosage forms
ES2581323T3 (en) 2010-12-23 2016-09-05 Purdue Pharma Lp Solid oral dosage forms resistant to alterations
US8927010B2 (en) 2011-03-23 2015-01-06 Ironshore Pharmaceuticals & Development, Inc. Compositions for treatment of attention deficit hyperactivity disorder
US8916588B2 (en) 2011-03-23 2014-12-23 Ironshore Pharmaceuticals & Development, Inc. Methods for treatment of attention deficit hyperactivity disorder
US9119809B2 (en) 2011-03-23 2015-09-01 Ironshore Pharmaceuticals & Development, Inc. Compositions for treatment of attention deficit hyperactivity disorder
US10292937B2 (en) 2011-03-23 2019-05-21 Ironshore Pharmaceuticals & Development, Inc. Methods of treatment of attention deficit hyperactivity disorder
US9603809B2 (en) 2011-03-23 2017-03-28 Ironshore Pharmaceuticals & Development, Inc. Methods of treatment of attention deficit hyperactivity disorder
US9498447B2 (en) 2011-03-23 2016-11-22 Ironshore Pharmaceuticals & Development, Inc. Compositions for treatment of attention deficit hyperactivity disorder
SG193587A1 (en) 2011-03-23 2013-10-30 Ironshore Pharmaceuticals & Dev Inc Methods and compositions for treatment of attention deficit disorder
US10905652B2 (en) 2011-03-23 2021-02-02 Ironshore Pharmaceuticals & Development, Inc. Compositions for treatment of attention deficit hyperactivity disorder
US11241391B2 (en) 2011-03-23 2022-02-08 Ironshore Pharmaceuticals & Development, Inc. Compositions for treatment of attention deficit hyperactivity disorder
US9283214B2 (en) 2011-03-23 2016-03-15 Ironshore Pharmaceuticals & Development, Inc. Compositions for treatment of attention deficit hyperactivity disorder
US9566241B2 (en) 2012-02-21 2017-02-14 Auburn University Buprenorphine nanoparticle composition and methods thereof
EP3446685A1 (en) 2012-11-30 2019-02-27 Acura Pharmaceuticals, Inc. Self-regulated release of active pharmaceutical ingredient
US9149533B2 (en) 2013-02-05 2015-10-06 Purdue Pharma L.P. Tamper resistant pharmaceutical formulations
US10751287B2 (en) 2013-03-15 2020-08-25 Purdue Pharma L.P. Tamper resistant pharmaceutical formulations
US9770514B2 (en) 2013-09-03 2017-09-26 ExxPharma Therapeutics LLC Tamper-resistant pharmaceutical dosage forms
US20150118300A1 (en) 2013-10-31 2015-04-30 Cima Labs Inc. Immediate Release Abuse-Deterrent Granulated Dosage Forms
CA2938699A1 (en) 2014-02-05 2015-08-13 Kashiv Pharma Llc Abuse-resistant drug formulations with built-in overdose protection
EP3122336A4 (en) 2014-03-26 2017-10-25 Sun Pharma Advanced Research Company Ltd Abuse deterrent immediate release biphasic matrix solid dosage form
CA2910865C (en) 2014-07-15 2016-11-29 Isa Odidi Compositions and methods for reducing overdose
US9132096B1 (en) 2014-09-12 2015-09-15 Alkermes Pharma Ireland Limited Abuse resistant pharmaceutical compositions
US11103581B2 (en) 2015-08-31 2021-08-31 Acura Pharmaceuticals, Inc. Methods and compositions for self-regulated release of active pharmaceutical ingredient
US9943513B1 (en) 2015-10-07 2018-04-17 Banner Life Sciences Llc Opioid abuse deterrent dosage forms
US20180303757A1 (en) 2015-10-23 2018-10-25 Kashiv Pharma Llc Enhanced abuse-deterrent formulations of oxycodone
EP3181124A1 (en) 2015-12-16 2017-06-21 Universität Basel Abuse deterrent pharmaceutical dosage forms
US10624888B2 (en) 2016-03-31 2020-04-21 SpecGx LLC Extended release, abuse deterrent dosage forms
US10335405B1 (en) 2016-05-04 2019-07-02 Patheon Softgels, Inc. Non-burst releasing pharmaceutical composition
US9737530B1 (en) 2016-06-23 2017-08-22 Collegium Pharmaceutical, Inc. Process of making stable abuse-deterrent oral formulations
US10335375B2 (en) 2017-05-30 2019-07-02 Patheon Softgels, Inc. Anti-overingestion abuse deterrent compositions
US10869838B2 (en) 2017-10-10 2020-12-22 Douglas Pharmaceuticals, Ltd. Extended release pharmaceutical formulation
US11471415B2 (en) 2017-10-10 2022-10-18 Douglas Pharmaceuticals, Ltd. Extended release pharmaceutical formulation and methods of treatment
US10441544B2 (en) 2017-10-10 2019-10-15 Douglas Pharmaceuticals, Ltd. Extended release pharmaceutical formulation
EP3473246A1 (en) 2017-10-19 2019-04-24 Capsugel Belgium NV Immediate release abuse deterrent formulations
EP3965733A4 (en) 2019-05-07 2023-01-11 Clexio Biosciences Ltd. Abuse-deterrent dosage forms containing esketamine

Citations (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3865108A (en) * 1971-05-17 1975-02-11 Ortho Pharma Corp Expandable drug delivery device
US3980766A (en) * 1973-08-13 1976-09-14 West Laboratories, Inc. Orally administered drug composition for therapy in the treatment of narcotic drug addiction
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
US4207893A (en) * 1977-08-29 1980-06-17 Alza Corporation Device using hydrophilic polymer for delivering drug to biological environment
US4262017A (en) * 1978-05-22 1981-04-14 Basf Aktiengesellschaft Preparation of a vitamin E dry powder
US4343789A (en) * 1979-07-05 1982-08-10 Yamanouchi Pharmaceutical Co., Ltd. Sustained release pharmaceutical composition of solid medical material
US4427681A (en) * 1982-09-16 1984-01-24 Richardson-Vicks, Inc. Thixotropic compositions easily convertible to pourable liquids
US4603143A (en) * 1983-05-02 1986-07-29 Basf Corporation Free-flowing, high density, fat soluble vitamin powders with improved stability
US4612008A (en) * 1983-05-11 1986-09-16 Alza Corporation Osmotic device with dual thermodynamic activity
US4765989A (en) * 1983-05-11 1988-08-23 Alza Corporation Osmotic device for administering certain drugs
US4783337A (en) * 1983-05-11 1988-11-08 Alza Corporation Osmotic system comprising plurality of members for dispensing drug
US4892889A (en) * 1986-11-18 1990-01-09 Basf Corporation Process for making a spray-dried, directly-compressible vitamin powder comprising unhydrolyzed gelatin
US5460826A (en) * 1994-06-27 1995-10-24 Alza Corporation Morphine therapy
US5556640A (en) * 1991-02-28 1996-09-17 Showa Yakuhin Kako Co., Ltd. Dry gel composition
US5601842A (en) * 1993-09-03 1997-02-11 Gruenenthal Gmbh Sustained release drug formulation containing a tramadol salt
US5792474A (en) * 1992-05-22 1998-08-11 Goedecke Aktiengesellschaft Process for the production of retarded pharmaceutical compositions
US5811126A (en) * 1995-10-02 1998-09-22 Euro-Celtique, S.A. Controlled release matrix for pharmaceuticals
US5968925A (en) * 1995-06-23 1999-10-19 Boeters & Bauer Process for continuous sintering of granules
US6228863B1 (en) * 1997-12-22 2001-05-08 Euro-Celtique S.A. Method of preventing abuse of opioid dosage forms
US6245357B1 (en) * 1998-03-06 2001-06-12 Alza Corporation Extended release dosage form
US6261599B1 (en) * 1994-11-04 2001-07-17 Euro-Celtique, S.A. Melt-extruded orally administrable opioid formulations
US6309668B1 (en) * 1994-02-01 2001-10-30 Aventis Pharma Limited Abuse resistant tablets
US6821588B1 (en) * 1998-05-25 2004-11-23 Kalle Gmbh & Co. Kg Film containing starch or starch derivatives and polyester urethanes
US20050191244A1 (en) * 2002-10-25 2005-09-01 Gruenenthal Gmbh Abuse-resistant pharmaceutical dosage form
US7776314B2 (en) * 2002-06-17 2010-08-17 Grunenthal Gmbh Abuse-proofed dosage system
US7812169B2 (en) * 2000-11-30 2010-10-12 The Children's Medical Center Corporation Method of synthesis of 4-amino-thalidomide enantiomers

Family Cites Families (539)

* 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
US630668A (en) * 1899-03-27 1899-08-08 Harry E Dade Binder.
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
US3806603A (en) 1969-10-13 1974-04-23 W Gaunt Pharmaceutical carriers of plasticized dried milled particles of hydrated cooked rice endosperm
CH503520A (en) 1969-12-15 1971-02-28 Inventa Ag Process for grinding granular materials, in particular plastic granulates, at low temperatures
DE2210071A1 (en) 1971-03-09 1972-09-14 PPG Industries Inc., Pittsburgh, Pa. (V.StA.) Process for applying and curing a wide variety of coatings
US3966747A (en) 1972-10-26 1976-06-29 Bristol-Myers Company 9-Hydroxy-6,7-benzomorphans
US4014965A (en) 1972-11-24 1977-03-29 The Dow Chemical Company Process for scrapless forming of plastic articles
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
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
US4200704A (en) 1978-09-28 1980-04-29 Union Carbide Corporation Controlled degradation of poly(ethylene oxide)
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
CH648754A5 (en) 1979-08-16 1985-04-15 Ciba Geigy Ag Pharmaceutical slow release tablet
US4353887A (en) 1979-08-16 1982-10-12 Ciba-Geigy Corporation Divisible tablet having controlled and delayed release of the active substance
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
US5082668A (en) 1983-05-11 1992-01-21 Alza Corporation Controlled-release system with constant pushing source
US4599342A (en) 1984-01-16 1986-07-08 The Procter & Gamble Company Pharmaceutical products providing enhanced analgesia
US4629621A (en) 1984-07-23 1986-12-16 Zetachron, Inc. Erodible matrix for sustained release bioactive composition
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
WO1987000045A1 (en) 1985-06-24 1987-01-15 Ici Australia Limited Ingestible capsules
AU607681B2 (en) 1985-06-28 1991-03-14 Carrington Laboratories, Inc. Processes for preparation of aloe products, products produced thereby and compositions thereof
US4992279A (en) 1985-07-03 1991-02-12 Kraft General Foods, Inc. Sweetness inhibitor
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
US5198226A (en) 1986-01-30 1993-03-30 Syntex (U.S.A.) Inc. Long acting nicardipine hydrochloride formulation
US4764378A (en) 1986-02-10 1988-08-16 Zetachron, Inc. Buccal drug dosage form
JPS62232433A (en) 1986-03-31 1987-10-12 ユニオン、カ−バイド、コ−ポレ−シヨン Catalyst to polymerization of alkylene oxide and polymerization
DE3612211A1 (en) 1986-04-11 1987-10-15 Basf Ag CONTINUOUS TABLET METHOD
US4667013A (en) 1986-05-02 1987-05-19 Union Carbide Corporation Process for alkylene oxide polymerization
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
AU622610B2 (en) 1986-11-10 1992-04-16 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
DE3868077D1 (en) 1987-01-14 1992-03-12 Ciba Geigy Ag THERAPEUTIC SYSTEM FOR HEAVY-SOLUBLE ACTIVE SUBSTANCES.
US4892778A (en) 1987-05-27 1990-01-09 Alza Corporation Juxtaposed laminated arrangement
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
US5004601A (en) 1988-10-14 1991-04-02 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
US5200197A (en) 1989-11-16 1993-04-06 Alza Corporation Contraceptive pill
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
SU1759445A1 (en) 1990-06-15 1992-09-07 Ленинградский Технологический Институт Им.Ленсовета Method of producing encapsulated hydrophobic substances
FR2664851B1 (en) 1990-07-20 1992-10-16 Oreal METHOD OF COMPACTING A POWDER MIXTURE FOR OBTAINING A COMPACT ABSORBENT OR PARTIALLY DELITABLE PRODUCT AND PRODUCT OBTAINED BY THIS PROCESS.
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
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
ATE183642T1 (en) 1991-10-04 1999-09-15 Yoshitomi Pharmaceutical DELAYED-RELEASE TABLET
WO1993006723A1 (en) 1991-10-04 1993-04-15 Olin Corporation Fungicide tablet
DE4138513A1 (en) 1991-11-23 1993-05-27 Basf Ag SOLID PHARMACEUTICAL RETARD FORM
US5266331A (en) 1991-11-27 1993-11-30 Euroceltique, S.A. Controlled release oxycodone compositions
DK0615438T3 (en) 1991-12-05 1996-11-11 Mallinckrodt Veterinary Inc A carbohydrate glass matrix for long-term release of a therapeutic agent
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
US5200194A (en) 1991-12-18 1993-04-06 Alza Corporation Oral osmotic device
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
GB9217295D0 (en) 1992-08-14 1992-09-30 Wellcome Found Controlled released tablets
DE4227385A1 (en) 1992-08-19 1994-02-24 Kali Chemie Pharma Gmbh Pancreatin micropellets
DE4229085C2 (en) 1992-09-01 1996-07-11 Boehringer Mannheim Gmbh Elongated, divisible tablet
HU226456B1 (en) 1992-09-18 2008-12-29 Astellas Pharma Inc Sustained-release hydrogel preparation
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
AU683044B2 (en) 1992-12-23 1997-10-30 Saitec S.R.L. Process for preparing controlled release pharmaceutical forms and the forms thus obtained
GB2273874A (en) 1992-12-31 1994-07-06 Pertti Olavi Toermaelae Preparation of pharmaceuticals in a polymer matrix
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
EP0647448A1 (en) 1993-10-07 1995-04-12 Euroceltique S.A. Orally administrable opioid formulations having extended duration of effect
DK0654263T3 (en) 1993-11-23 2002-04-29 Euro Celtique Sa Process for the preparation of a sustained release preparation
KR100354702B1 (en) 1993-11-23 2002-12-28 유로-셀티크 소시에떼 아노뉨 Manufacturing method and sustained release composition of pharmaceutical 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
MX9603480A (en) 1994-02-16 1997-12-31 Abbott Lab 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
RO114740B1 (en) 1994-05-06 1999-07-30 Pfizer Controlled release composition, process for preparing the same and method of treatment
DE19509807A1 (en) 1995-03-21 1996-09-26 Basf Ag Process for the preparation of active substance preparations in the form of a solid solution of the active substance in a polymer matrix, and active substance preparations produced using this method
AT403988B (en) 1994-05-18 1998-07-27 Lannacher Heilmittel SOLID ORAL RETARDED PREPARATION
DE4426245A1 (en) 1994-07-23 1996-02-22 Gruenenthal Gmbh 1-phenyl-3-dimethylamino-propane compounds with pharmacological activity
IT1274879B (en) 1994-08-03 1997-07-25 Saitec Srl APPARATUS AND METHOD FOR PREPARING SOLID PHARMACEUTICAL FORMS WITH CONTROLLED RELEASE OF THE ACTIVE INGREDIENT.
JP3285452B2 (en) 1994-08-11 2002-05-27 サンスター株式会社 Toothpaste composition
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
DE4446470A1 (en) 1994-12-23 1996-06-27 Basf Ag Process for the production of dividable tablets
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
US6348469B1 (en) 1995-04-14 2002-02-19 Pharma Pass Llc Solid compositions containing glipizide and polyethylene oxide
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
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
DE19539361A1 (en) 1995-10-23 1997-04-24 Basf Ag Process for the preparation of multilayer, solid pharmaceutical forms for oral or rectal administration
US6355656B1 (en) 1995-12-04 2002-03-12 Celgene Corporation Phenidate drug formulations having diminished abuse potential
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
DK0914097T3 (en) 1996-03-12 2002-04-29 Alza Corp Composition and dosage form comprising opioid antagonist
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
EP0914158B2 (en) 1996-04-05 2006-01-25 Takeda Chemical Industries, Ltd. Pharmaceutical combination containing a compound having angiotensin ii antagonistic activity and a compound which increases the insulin-sensitivity
US6096339A (en) 1997-04-04 2000-08-01 Alza Corporation Dosage form, process of making and using same
US5817343A (en) 1996-05-14 1998-10-06 Alkermes, Inc. Method for fabricating polymer-based controlled-release devices
WO1997046224A1 (en) 1996-06-06 1997-12-11 Bifodan A/S Enteric coating, comprising alginic acid, for an oral preparation
ATE427124T1 (en) 1996-06-26 2009-04-15 Univ Texas HOT-MELTED EXTRUDABLE PHARMACEUTICAL FORMULATION
US6093420A (en) 1996-07-08 2000-07-25 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.
ATE287928T1 (en) 1996-11-05 2005-02-15 Novamont Spa BIODEGRADABLE POLYMER COMPOSITIONS CONTAINING STARCH AND A THERMOPLASTIC POLYMER
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
ATE302597T1 (en) 1997-06-06 2005-09-15 Depomed Inc STOMACH-RESIDENT ORAL DOSAGE FORMS OF WATER-SOLUBLE DRUGS WITH CONTROLLED RELEASE
ATE322892T1 (en) 1997-07-02 2006-04-15 Euro Celtique Sa STABILIZED SUSTAINED-RELEASE TRAMADOL FORMULATIONS
IE970588A1 (en) 1997-08-01 2000-08-23 Elan Corp Plc Controlled release pharmaceutical compositions containing tiagabine
CA2303036A1 (en) 1997-09-10 1999-03-18 Alliedsignal Inc. Injection molding of structural zirconia-based materials by an aqueous process
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
PT1033975E (en) 1997-11-28 2002-07-31 Knoll Ag PROCESS FOR THE PREPARATION OF BIOLOGICALLY ACTIVE NAO-CRYSTALLINE SUBSTANCES ISSUED OF DISSOLVENTS
EP1036107A1 (en) 1997-12-03 2000-09-20 Basf Aktiengesellschaft Polyether ester amides
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
US6375957B1 (en) 1997-12-22 2002-04-23 Euro-Celtique, S.A. Opioid agonist/opioid antagonist/acetaminophen combinations
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
WO1999040156A1 (en) 1998-02-06 1999-08-12 Union Carbide Chemicals & Plastics Technology Corporation Alkylene oxide polymer compositions
DE69918233T2 (en) 1998-03-05 2005-02-24 Mitsui Chemicals, Inc. POLYMIC ACID COMPOSITION AND FILM MANUFACTURED THEREOF
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
JP2002510878A (en) 1998-04-02 2002-04-09 アプライド マテリアルズ インコーポレイテッド Method for etching a low-k dielectric
ES2221370T3 (en) 1998-04-03 2004-12-16 Egalet A/S COMPOSITION OF CONTROLLED RELEASE.
US5962488A (en) 1998-04-08 1999-10-05 Roberts Laboratories, Inc. Stable pharmaceutical formulations for treating internal bowel syndrome containing isoxazole derivatives
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
WO2000023073A1 (en) 1998-10-20 2000-04-27 Korea Institute Of Science And Technology 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
DE19856147A1 (en) 1998-12-04 2000-06-08 Knoll Ag Divisible solid dosage forms and methods for their preparation
EP1005863A1 (en) 1998-12-04 2000-06-07 Synthelabo Controlled-release dosage forms comprising a short acting hypnotic or a salt thereof
US6238697B1 (en) 1998-12-21 2001-05-29 Pharmalogix, Inc. Methods and formulations for making bupropion hydrochloride tablets using direct compression
WO2000040205A2 (en) 1999-01-05 2000-07-13 Copley Pharmaceutical Inc. Sustained release formulation with reduced moisture sensitivity
CN1145493C (en) 1999-02-04 2004-04-14 尼基摩株式会社 Materials for preventing arteriosclerosis, Immunopotentiating meterials, vertegrates 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
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
US6384020B1 (en) 1999-07-14 2002-05-07 Shire Laboratories, Inc. Rapid immediate release oral dosage form
JP2003522127A (en) 1999-07-29 2003-07-22 ロクセニ ラボラトリーズ インコーポレイテッド Opioid sustained release formulation
US20030118641A1 (en) 2000-07-27 2003-06-26 Roxane Laboratories, Inc. Abuse-resistant sustained-release opioid formulation
ATE324909T1 (en) 1999-08-04 2006-06-15 Astellas Pharma Inc STABLE MEDICAL COMPOSITIONS FOR ORAL ADMINISTRATION USING IRON OXIDES
US6562375B1 (en) 1999-08-04 2003-05-13 Yamanouchi Pharmaceuticals, Co., Ltd. Stable pharmaceutical composition for oral use
KR100345214B1 (en) 1999-08-17 2002-07-25 이강춘 The nasal transmucosal delivery of peptides conjugated with biocompatible polymers
DE19940944B4 (en) 1999-08-31 2006-10-12 Grünenthal GmbH Retarded, oral, pharmaceutical dosage forms
MXPA02002193A (en) 1999-08-31 2002-09-30 Gr Nenthal Gmbh Delayedaction form of administration containing tramadol saccharinate.
DE19940740A1 (en) 1999-08-31 2001-03-01 Gruenenthal Gmbh Pharmaceutical salts
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
DK1299104T3 (en) 2000-02-08 2009-08-03 Euro Celtique Sa Oral opioid agonist formulations secured against forgery
US20020015730A1 (en) 2000-03-09 2002-02-07 Torsten Hoffmann Pharmaceutical formulations and method for making
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
AU2001274947B2 (en) 2000-05-23 2006-08-17 Acorda Therapeutics, Inc. Nrg-2 nucleic acid molecules, polypeptides, and diagnostic and therapeutic methods
DE10029201A1 (en) 2000-06-19 2001-12-20 Basf Ag Retarded release oral dosage form, obtained by granulating mixture containing active agent and polyvinyl acetate-polyvinyl pyrrolidone mixture below the melting temperature
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
EP1363673A2 (en) 2000-09-25 2003-11-26 Pro-Pharmaceuticals, Inc. Compositions for reducing side effects in chemotherapeutic treatments
WO2002026061A1 (en) 2000-09-27 2002-04-04 Danisco A/S Antimicrobial agent
AU2001294902A1 (en) 2000-09-28 2002-04-08 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
WO2002035991A2 (en) 2000-10-30 2002-05-10 The Board Of Regents, The University Of Texas System Spherical particles produced by a hot-melt extrusion/spheronization process
WO2002036099A1 (en) 2000-10-30 2002-05-10 Euro-Celtique S.A. Controlled release hydrocodone formulations
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
US20020187192A1 (en) 2001-04-30 2002-12-12 Yatindra Joshi Pharmaceutical composition which reduces or eliminates drug abuse potential
ES2260437T3 (en) 2001-05-01 2006-11-01 UNION CARBIDE CHEMICALS & PLASTICS TECHNOLOGY CORPORATION PHARMACEUTICAL COMPOSITION THAT INCLUDES POLI (ALKYLENE OXIDES) THAT HAVE 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
US20030065002A1 (en) 2001-05-11 2003-04-03 Endo Pharmaceuticals, Inc. 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
US20030008409A1 (en) 2001-07-03 2003-01-09 Spearman Steven R. Method and apparatus for determining sunlight exposure
BR0210855A (en) 2001-07-06 2006-10-24 Penwest Pharmaceuticals Compan Method of Manufacturing Extended Release Formulations
US8329216B2 (en) 2001-07-06 2012-12-11 Endo Pharmaceuticals Inc. Oxymorphone controlled release formulations
CA2452871C (en) 2001-07-06 2011-10-04 Endo Pharmaceuticals, Inc. Oxymorphone controlled release formulations
JP2003020517A (en) 2001-07-10 2003-01-24 Calp Corp Resin composition for compound fiber
JP4256259B2 (en) 2001-07-18 2009-04-22 ユーロ−セルティーク エス．エイ． Pharmaceutical formulation of oxycodone and naloxone
US6883976B2 (en) 2001-07-30 2005-04-26 Seikoh Giken Co., Ltd. Optical fiber ferrule assembly and optical module and optical connector using the same
US7842307B2 (en) 2001-08-06 2010-11-30 Purdue Pharma L.P. Pharmaceutical formulation containing opioid agonist, opioid antagonist and gelling agent
US20030157168A1 (en) 2001-08-06 2003-08-21 Christopher Breder Sequestered antagonist formulations
US7144587B2 (en) 2001-08-06 2006-12-05 Euro-Celtique S.A. Pharmaceutical formulation containing opioid agonist, opioid antagonist and bittering agent
HUP0401344A2 (en) 2001-08-06 2004-11-29 Euro-Celtique S.A. Pharmaceutical compositions to prevent abuse of opioids and process for producing them
US7332182B2 (en) 2001-08-06 2008-02-19 Purdue Pharma L.P. Pharmaceutical formulation containing opioid agonist, opioid antagonist and irritant
US7141250B2 (en) 2001-08-06 2006-11-28 Euro-Celtique S.A. Pharmaceutical formulation containing bittering agent
US7157103B2 (en) 2001-08-06 2007-01-02 Euro-Celtique S.A. Pharmaceutical formulation containing irritant
US20030068375A1 (en) 2001-08-06 2003-04-10 Curtis Wright Pharmaceutical formulation containing gelling agent
US20030044458A1 (en) 2001-08-06 2003-03-06 Curtis Wright Oral dosage form comprising a therapeutic agent and an adverse-effect agent
AU2002321879A1 (en) 2001-08-06 2003-03-03 Thomas Gruber Pharmaceutical formulation containing dye
BR0212019A (en) 2001-08-06 2005-08-09 Euro Celtique Sa Dosage forms, methods for treating pain, methods of preparing a dosage form and methods for preventing abuse of a dosage form.
US20030049272A1 (en) 2001-08-30 2003-03-13 Yatindra Joshi Pharmaceutical composition which produces irritation
US20030059467A1 (en) 2001-09-14 2003-03-27 Pawan Seth Pharmaceutical composition comprising doxasozin
US6691698B2 (en) 2001-09-14 2004-02-17 Fmc Technologies Inc. Cooking oven having curved heat exchanger
US20030059397A1 (en) 2001-09-17 2003-03-27 Lyn Hughes Dosage forms
US20030068276A1 (en) 2001-09-17 2003-04-10 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
ES2298401T3 (en) 2001-09-21 2008-05-16 Egalet A/S SOLID DISPERSIONS OF CONTROLLED LIBERATION OF CARVEDILOL.
US20040253310A1 (en) 2001-09-21 2004-12-16 Gina Fischer Morphine polymer release system
AU2002337686B2 (en) 2001-09-26 2008-05-15 Penwest Pharmaceuticals Company Opioid formulations having reduced potential for abuse
WO2003028698A2 (en) 2001-09-26 2003-04-10 Steffens Klaus-Juergen 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
BR0212951A (en) 2001-09-28 2004-10-26 Mcneil Ppc Inc Composite Dosage Forms
ES2261741T3 (en) 2001-10-09 2006-11-16 THE PROCTER & GAMBLE COMPANY WATERPROOF COMPOSITIONS TO TREAT A SURFACE.
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
PE20030527A1 (en) 2001-10-24 2003-07-26 Gruenenthal Chemie DELAYED-RELEASE PHARMACEUTICAL FORMULATION CONTAINING 3- (3-DIMETHYLAMINO-1-ETHYL-2-METHYL-PROPYL) PHENOL OR A PHARMACEUTICALLY ACCEPTABLE SALT OF THE SAME AND ORAL TABLETS CONTAINING IT
CA2409552A1 (en) 2001-10-25 2003-04-25 Depomed, Inc. Gastric retentive oral dosage form with restricted drug release in the lower gastrointestinal tract
US20030104052A1 (en) 2001-10-25 2003-06-05 Bret Berner 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
TWI312285B (en) 2001-10-25 2009-07-21 Depomed Inc Methods of treatment using a gastric retained gabapentin dosage
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
JP4551089B2 (en) 2001-10-29 2010-09-22 マサチューセッツ インスティテュート オブ テクノロジー System for producing sustained release dosage forms such as zero order release profile dosage forms produced by three-dimensional printing
US20030125347A1 (en) 2001-11-02 2003-07-03 Elan Corporation Plc Pharmaceutical composition
US20040126428A1 (en) 2001-11-02 2004-07-01 Lyn Hughes Pharmaceutical formulation including a resinate and an aversive agent
AU2002366638A1 (en) 2001-12-06 2003-06-23 Scolr Pharma, Inc. 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
CA2708900C (en) 2002-04-05 2019-06-04 Purdue Pharma 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
US20050106249A1 (en) 2002-04-29 2005-05-19 Stephen Hwang Once-a-day, oral, controlled-release, oxycodone dosage forms
BR0309620A (en) 2002-04-29 2005-03-15 Alza Corp Methods and dosage forms for controlled release of oxycodone
US20030224051A1 (en) 2002-05-31 2003-12-04 Fink Tracy A. Dosage forms and compositions for osmotic delivery of variable dosages of oxycodone
AU2003234395B2 (en) 2002-05-13 2008-01-24 Endo Pharmaceuticals Inc. Abuse-resistant opioid solid dosage form
DE10250083A1 (en) 2002-06-17 2003-12-24 Gruenenthal Gmbh Dosage form protected against abuse
CA2491572C (en) 2002-07-05 2010-03-23 Collegium Pharmaceutical, Inc. Abuse-deterrent pharmaceutical compositions of opiods and other drugs
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
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
EP1539112A1 (en) 2002-08-21 2005-06-15 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
US20040052844A1 (en) 2002-09-16 2004-03-18 Fang-Hsiung Hsiao Time-controlled, sustained release, pharmaceutical composition containing water-soluble resins
EP1545600A4 (en) 2002-09-16 2006-07-12 Advanced Bionutrition Corp Protein and peptide expression for passive immunity
DK1635830T3 (en) 2002-09-17 2009-02-23 Wyeth Corp Granulation formulation of the rapamycin ester CCI-779
WO2004026263A2 (en) 2002-09-20 2004-04-01 Fmc Corporation Cosmetic composition containing microcrystalline cellulose
AU2003271024A1 (en) 2002-09-21 2004-04-08 Jin Wang Sustained release compound of acetamidophenol and tramadol
CA2499994C (en) 2002-09-23 2012-07-10 Verion, Inc. Abuse-resistant pharmaceutical compositions
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
DE10250088A1 (en) 2002-10-25 2004-05-06 Grünenthal GmbH Dosage form protected against abuse
DE10250087A1 (en) 2002-10-25 2004-05-06 Grünenthal GmbH Dosage form protected against abuse
US20050186139A1 (en) 2002-10-25 2005-08-25 Gruenenthal Gmbh Abuse-proofed dosage form
DE10250084A1 (en) 2002-10-25 2004-05-06 Grünenthal GmbH Dosage form protected against abuse
KR20050083816A (en) 2002-10-25 2005-08-26 라보팜 인코포레이트 Sustained-release tramadol formulations with 24-hour efficacy
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
US20040091528A1 (en) 2002-11-12 2004-05-13 Yamanouchi Pharma Technologies, Inc. Soluble drug extended release system
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
EP1610767B1 (en) 2003-03-26 2011-01-19 Egalet A/S Morphine controlled release system
WO2004084869A1 (en) 2003-03-26 2004-10-07 Egalet A/S Matrix compositions for controlled delivery of drug substances
MY135852A (en) 2003-04-21 2008-07-31 Euro Celtique Sa Pharmaceutical products
JP5501553B2 (en) 2003-04-21 2014-05-21 ユーロ−セルティーク エス．エイ． Anti-modified dosage form containing coextrusion adverse agent particles and process
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
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
DE10336400A1 (en) 2003-08-06 2005-03-24 Grünenthal GmbH Anti-abuse dosage form
DE102004020220A1 (en) 2004-04-22 2005-11-10 Grünenthal GmbH Process for the preparation of a secured against misuse, solid dosage form
ATE365545T1 (en) 2003-08-06 2007-07-15 Gruenenthal Gmbh DOSAGE FORM PROVEN AGAINST ABUSE
RU2339365C2 (en) 2003-08-06 2008-11-27 Грюненталь Гмбх Drug dosage form, protected from unintended application
CL2004002016A1 (en) 2003-08-06 2005-05-20 Gruenenthal Chemie THERMOFORMED DOSAGE FORM FOR PROOF OF ABUSE CONTAINING (A) ONE OR MORE SUSCEPTIBLE ACTIVE PRINCIPLES OF ABUSE, (B) OPTIONALLY AUXILIARY SUBSTANCES, (C) AT LEAST A DEFINED SYNTHETIC OR NATURAL POLYMER AND (D) OPTIONALLY AT LEAST
DE10361596A1 (en) 2003-12-24 2005-09-29 Grünenthal GmbH Process for producing an anti-abuse dosage form
DE102004032051A1 (en) 2004-07-01 2006-01-19 Grünenthal GmbH Process for the preparation of a secured against misuse, solid dosage form
US20070048228A1 (en) 2003-08-06 2007-03-01 Elisabeth Arkenau-Maric Abuse-proofed dosage form
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
US20050063214A1 (en) 2003-09-22 2005-03-24 Daisaburo Takashima Semiconductor integrated circuit device
CA2539027C (en) 2003-09-25 2010-02-23 Euro-Celtique S.A. Pharmaceutical combinations of hydrocodone and naltrexone
WO2005032524A2 (en) 2003-09-30 2005-04-14 Alza Corporation Osmotically driven active agent delivery device providing an ascending 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
CN1933837A (en) 2003-10-29 2007-03-21 阿尔扎公司 Once-a-day, oral, controlled-release, oxycodone dosage forms
US7201920B2 (en) 2003-11-26 2007-04-10 Acura Pharmaceuticals, Inc. Methods and compositions for deterring abuse of opioid containing dosage forms
JP2007513147A (en) 2003-12-04 2007-05-24 ファイザー・プロダクツ・インク Spray congealing process for producing a multiparticulate crystalline pharmaceutical composition, preferably containing poloxamer and glyceride, using an extruder
US20070269505A1 (en) 2003-12-09 2007-11-22 Flath Robert P 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
CA2551815A1 (en) 2003-12-29 2005-07-21 Alza Corporation Novel drug compositions and dosage forms
EP1750717B1 (en) 2004-02-11 2017-07-19 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
PL2351555T3 (en) 2004-02-23 2017-06-30 Euro-Celtique S.A. Abuse resistance opioid transdermal delivery device
TW201509943A (en) 2004-03-30 2015-03-16 Euro Celtique Sa Oxycodone hydrochloride composition, pharmaceutical dosage form, sustained release oral dosage form and pharmaceutically acceptable package having less than 25 PPM 14-hydroxycodeinone
US20050220877A1 (en) 2004-03-31 2005-10-06 Patel Ashish A Bilayer tablet comprising an antihistamine and a decongestant
DE102004019916A1 (en) 2004-04-21 2005-11-17 Grünenthal GmbH Anti-abuse drug-containing patch
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
SI1612203T1 (en) 2004-06-28 2007-12-31 Gruenenthal Chemie 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
WO2006002886A1 (en) 2004-07-01 2006-01-12 Grünenthal GmbH Oral dosage form safeguarded against abuse containing (1r, 2r)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol
DE102004032103A1 (en) 2004-07-01 2006-01-19 Grünenthal GmbH Anti-abuse, oral dosage form
DE102004032049A1 (en) 2004-07-01 2006-01-19 Grünenthal GmbH Anti-abuse, oral dosage form
WO2006002883A1 (en) 2004-07-01 2006-01-12 Grünenthal GmbH Method for producing a solid dosage form, which is safeguarded against abuse, while using a planetary gear extruder
EP1765303B2 (en) 2004-07-01 2022-11-23 Grünenthal GmbH Oral tablet safeguarded against abuse
DE602005007237D1 (en) 2004-07-27 2008-07-10 Unilever Nv HAIR CARE COMPOSITIONS
US20070077297A1 (en) 2004-09-30 2007-04-05 Scolr Pharma, Inc. Modified release ibuprofen dosage form
US20060068009A1 (en) 2004-09-30 2006-03-30 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
SI1849470T1 (en) 2005-01-26 2017-10-30 Taiho Pharmaceutical Co., Ltd. Anticancer drug containing alpha, alpha, alpha-trifluorothymidine and thymidine phosphorylase inhibitor
EP2319499A1 (en) 2005-01-28 2011-05-11 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
MX2007009281A (en) 2005-02-10 2007-09-25 Lufecycle Pharma As A stable pharmaceutical composition comprising a fixed dose combination of fenofibrate 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
PT1861405E (en) 2005-03-04 2009-07-27 Euro Celtique Sa Method of reducing alpha, beta- unsaturated ketones in opioid compositions
US7732427B2 (en) 2005-03-31 2010-06-08 University Of Delaware Multifunctional and biologically active matrices from multicomponent polymeric solutions
CN101227892B (en) 2005-04-08 2013-06-05 舌交付有限公司 Buccal delivery system
JP5400377B2 (en) 2005-05-10 2014-01-29 ノバルティス アーゲー Method for producing a composition having a therapeutic compound with poor compressibility
WO2006128471A2 (en) 2005-06-03 2006-12-07 Egalet A/S A solid pharmaceutical composition with a first fraction of a dispersion medium and a second fraction of a matrix, the latter being at least partially first exposed to gastrointestinal fluids
DE102005033272A1 (en) 2005-06-03 2006-12-07 Solartec Ag Concentrator photovoltaic device, PV concentrator module formed therefrom and manufacturing method thereof
WO2007005716A2 (en) 2005-06-30 2007-01-11 Cinergen, Llc Methods of treatment and compositions for use thereof
RU2008104638A (en) 2005-07-07 2009-08-20 Фарнэм Компаниз, Инк. (Us) PHARMACEUTICAL COMPOSITIONS OF WELL-SOLUBLE MEDICINAL PRODUCTS IN WATER, PROVIDING THEIR Slow-Motion Release
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
CN101232871A (en) 2005-08-03 2008-07-30 伊士曼化工公司 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
CN101326192B (en) 2005-10-14 2012-06-20 社团法人北里研究所 Novel dihydropseudoerythromycin derivatives
US20070092573A1 (en) 2005-10-24 2007-04-26 Laxminarayan Joshi Stabilized extended release pharmaceutical compositions comprising a beta-adrenoreceptor antagonist
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
WO2008134071A1 (en) 2007-04-26 2008-11-06 Theraquest Biosciences, Inc. Multimodal abuse resistant extended release formulations
US8329744B2 (en) 2005-11-02 2012-12-11 Relmada Therapeutics, Inc. Methods of preventing the serotonin syndrome and compositions for use thereof
FR2892937B1 (en) 2005-11-10 2013-04-05 Flamel Tech Sa MICROPARTICULAR ORAL PHARMACEUTICAL FORM ANTI-MEASURING
US8652529B2 (en) 2005-11-10 2014-02-18 Flamel Technologies Anti-misuse microparticulate oral pharmaceutical form
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
AU2007205866B2 (en) 2006-01-21 2012-11-29 Abbott Gmbh & Co. Kg Dosage form and method for the delivery of drugs of abuse
US20090022798A1 (en) 2007-07-20 2009-01-22 Abbott Gmbh & Co. Kg Formulations of nonopioid and confined opioid analgesics
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
PT1991522T (en) 2006-02-17 2016-08-23 Imphar Ag Deuterated catecholamine derivatives and medicaments comprising said compounds
ZA200807571B (en) 2006-03-01 2009-08-26 Ethypharm Sa Crush-resistant tablets intended to prevent accidental misuse and unlawful diversion
ATE448231T1 (en) 2006-03-02 2009-11-15 Mallinckrodt Inc METHOD FOR PRODUCING MORPHINAN-6-ONE PRODUCTS WITH LOW CONCENTRATIONS OF ALPHA-, BETA-UNSATURATED KETONE COMPOUNDS
US20100226855A1 (en) 2006-03-02 2010-09-09 Spherics, Inc. Rate-Controlled Oral Dosage Formulations
MX2008012264A (en) 2006-03-24 2009-02-20 Auxilium Int Holdings Inc Stabilized compositions containing alkaline labile drugs.
US8465759B2 (en) 2006-03-24 2013-06-18 Auxilium Us Holdings, Llc Process for the preparation of a hot-melt extruded laminate
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
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
CN101091721A (en) 2006-06-22 2007-12-26 孙明 Method for preparing new type asshide
WO2008008120A1 (en) 2006-07-14 2008-01-17 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
AU2007275034A1 (en) 2006-07-21 2008-01-24 Lab International Srl Hydrophilic abuse deterrent delivery system
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
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
US8187636B2 (en) 2006-09-25 2012-05-29 Atlantic Pharmaceuticals, Inc. Dosage forms for tamper prone therapeutic agents
KR20090113243A (en) 2006-10-10 2009-10-29 펜웨스트 파머슈티칼즈 컴파니 Robust sustained release formulations
US20080085304A1 (en) 2006-10-10 2008-04-10 Penwest Pharmaceuticals Co. Robust sustained release formulations
GB0624880D0 (en) 2006-12-14 2007-01-24 Johnson Matthey Plc Improved method for making analgesics
DE102006062120A1 (en) 2006-12-22 2008-06-26 Grünenthal GmbH Pharmaceutical composition for acne treatment
WO2008079404A2 (en) 2006-12-22 2008-07-03 Combinatorx, Incorporated Pharmaceutical compositions for treatment of parkinson's disease and related disorders
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
US20080181932A1 (en) 2007-01-30 2008-07-31 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
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
JP5452236B2 (en) 2007-03-02 2014-03-26 ファーナム・カンパニーズ・インコーポレーテッド Sustained release composition using wax-like substance
DE102007011485A1 (en) 2007-03-07 2008-09-11 Grünenthal GmbH Dosage form with more difficult abuse
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
EP2061587A1 (en) 2007-04-26 2009-05-27 Sigmoid Pharma Limited Manufacture of multiple minicapsules
WO2008142627A2 (en) 2007-05-17 2008-11-27 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
CA2687192C (en) 2007-06-04 2015-11-24 Egalet A/S Controlled release pharmaceutical compositions for prolonged effect
US20100035886A1 (en) 2007-06-21 2010-02-11 Veroscience, Llc Parenteral formulations of dopamine agonists
CA2690956C (en) 2007-07-01 2017-01-03 Joseph Peter Habboushe Combination tablet with chewable outer layer
RU2477995C2 (en) 2007-07-20 2013-03-27 Эбботт Гмбх Унд Ко.Кг Formulations of non-opioid and limited opioid analgesics
WO2009034541A2 (en) 2007-09-11 2009-03-19 Ranbaxy Laboratories Limited Controlled release pharmaceutical dosage forms of trimetazidine
PL2200593T3 (en) 2007-09-13 2017-02-28 Cima Labs Inc. Abuse resistant drug formulation
WO2009051819A1 (en) 2007-10-17 2009-04-23 Axxia Pharmaceuticals, Llc Polymeric drug delivery systems and thermoplastic extrusion processes for producing such systems
DK2596784T3 (en) 2007-11-23 2017-03-06 Gruenenthal Gmbh Tapentadol compositions
WO2009088414A2 (en) 2007-12-06 2009-07-16 Durect Corporation Oral pharmaceutical dosage forms
JP5646340B2 (en) 2007-12-12 2014-12-24 ビーエーエスエフ ソシエタス・ヨーロピアＢａｓｆ Ｓｅ Salts of polymeric counter ions and active ingredients
BRPI0821732A2 (en) 2007-12-17 2015-06-16 Labopharm Inc Controlled release formulations, solid dosage form, and use of controlled release formulation
RU2493830C2 (en) 2008-01-25 2013-09-27 Грюненталь Гмбх Drug form
KR100970665B1 (en) 2008-02-04 2010-07-15 삼일제약주식회사 Sustained release tablet containing alfuzosin or its salt
CA2717456A1 (en) 2008-03-05 2009-09-11 Panacea Biotec Limited Modified release pharmaceutical compositions comprising mycophenolate and processes thereof
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
EP2100598A1 (en) 2008-03-13 2009-09-16 Laboratorios Almirall, S.A. Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease
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
AU2009243681B2 (en) 2008-05-09 2013-12-19 Grunenthal Gmbh Process for the preparation of an intermediate powder formulation and a final solid dosage form under usage of a spray congealing step
CN102076329B (en) 2008-07-03 2013-03-06 诺瓦提斯公司 Melt granulation process
JP2012501967A (en) 2008-08-20 2012-01-26 ボード・オブ・リージエンツ，ザ・ユニバーシテイ・オブ・テキサス・システム Controlled release multiparticulate hot melt extrusion.
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
EP2345688B1 (en) 2008-10-24 2013-03-27 Kao Corporation Process for producing resin composition
US20100104638A1 (en) 2008-10-27 2010-04-29 Wei-Guo Dai Extended release oral acetaminophen/tramadol dosage form
CL2009002073A1 (en) 2008-11-14 2010-12-24 Portola Pharm Inc Solid pharmaceutical composition for the controlled release of an active active agent in the gastrointestinal tract comprising at least one acidic agent with solubility of less than 0.3 mg / ml in aqueous solution at a ph around the pka of the acidic agent, a hydrophilic polymer , an achiever; Use in cardiovascular disorders.
WO2010066034A1 (en) 2008-12-12 2010-06-17 Paladin Labs Inc. Methadone formulation
AU2009327312A1 (en) 2008-12-16 2011-08-04 Labopharm Europe Limited Misuse preventative, controlled release formulation
US20100203129A1 (en) 2009-01-26 2010-08-12 Egalet A/S Controlled release formulations with continuous efficacy
EP3184105A1 (en) 2009-02-06 2017-06-28 Egalet Ltd. Pharmaceutical compositions resistant to abuse
US9730899B2 (en) 2009-03-18 2017-08-15 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
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
PL2456427T3 (en) 2009-07-22 2015-07-31 Gruenenthal Gmbh Hot-melt extruded controlled release dosage form
EP2997965B1 (en) 2009-07-22 2019-01-02 Grünenthal GmbH Tamper-resistant dosage form for oxidation-sensitive opioids
CA2775890C (en) 2009-09-30 2016-06-21 Acura Pharmaceuticals, Inc. Methods and compositions for deterring abuse
WO2011059074A1 (en) 2009-11-13 2011-05-19 森六ケミカルズ株式会社 Fine powder manufacturing method and fine powder manufactured using same
EP2506838A1 (en) 2009-12-01 2012-10-10 Noven Pharmaceuticals, INC. Transdermal testosterone device and delivery
ES2606227T3 (en) 2010-02-03 2017-03-23 Grünenthal GmbH Preparation of a pharmaceutical powder composition by an extruder
EA029077B1 (en) 2010-03-09 2018-02-28 Алкермес Фарма Айэленд Лимитед Alcohol resistant pharmaceutical composition
JP5303496B2 (en) 2010-03-09 2013-10-02 日東電工株式会社 Optical waveguide device
WO2011123866A1 (en) 2010-04-02 2011-10-06 Alltranz Inc. Abuse-deterrent transdermal formulations of opiate agonists and agonist-antagonists
EP2555756B1 (en) 2010-04-07 2018-08-22 Lupin Limited Controlled release pharmaceutical compositions of tapentadol
GB201006200D0 (en) 2010-04-14 2010-06-02 Ayanda As Composition
PL2560624T3 (en) 2010-04-23 2019-01-31 Kempharm, Inc. Therapeutic formulation for reduced 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
AU2011297954B2 (en) 2010-09-02 2014-05-15 Grunenthal Gmbh Tamper resistant dosage form comprising an anionic polymer
MX2013002377A (en) 2010-09-02 2013-04-29 Gruenenthal Gmbh Tamper resistant dosage form comprising inorganic salt.
TWI516286B (en) 2010-09-02 2016-01-11 歌林達股份有限公司 Tamper resistant dosage form comprising an anionic polymer
EP2635258A1 (en) 2010-11-04 2013-09-11 AbbVie Inc. 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
ES2581323T3 (en) 2010-12-23 2016-09-05 Purdue Pharma Lp Solid oral dosage forms resistant to alterations
CN103476401A (en) 2011-02-17 2013-12-25 Qrx制药有限公司 Technology for preventing abuse of solid dosage forms
SI3287123T1 (en) 2011-03-04 2020-07-31 Gruenenthal Gmbh Aqueous pharmaceutical formulation of tapentadol for oral administration
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
CA2837077A1 (en) 2011-06-01 2012-12-06 Fmc Corporation Controlled release solid dose forms
US20140127300A1 (en) 2011-06-30 2014-05-08 Neos Therapeutics, Lp Abuse resistant drug forms
BR112014001091A2 (en) 2011-07-29 2017-02-14 Gruenenthal Gmbh tamper resistant tablet that provides immediate release of the drug
LT2736495T (en) 2011-07-29 2017-11-10 Grünenthal GmbH Tamper-resistant tablet providing immediate drug release
CA2844827A1 (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
PE20141171A1 (en) 2011-10-06 2014-09-21 Gruenenthal Chemie ORAL PHARMACEUTICAL DOSAGE FORM RESISTANT TO ALTERATION INCLUDING OPIOID AGONIST AND OPIOID ANTAGONIST
JP6085307B2 (en) 2011-11-17 2017-02-22 グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング Tamper resistant oral pharmaceutical dosage forms comprising pharmacologically active ingredients, opioid antagonists and / or aversive agents, polyalkylene oxides and anionic polymers
CN107854434A (en) 2011-12-09 2018-03-30 普渡制药公司 Include poly- (ε caprolactones) and polyoxyethylated pharmaceutical dosage form
JP2013155124A (en) 2012-01-30 2013-08-15 Moriroku Chemicals Co Ltd Bulk powder of medicine and method of producing the same
EP2819657A1 (en) 2012-02-28 2015-01-07 Grünenthal GmbH Tamper-resistant pharmaceutical dosage form comprising nonionic surfactant
BR112014019988A8 (en) 2012-02-28 2017-07-11 Gruenenthal Gmbh BREAK-RESISTANT DOSAGE FORM COMPRISING A PHARMACOLOGICALLY ACTIVE COMPOUND AND AN ANIONIC POLYMER
AR090218A1 (en) 2012-03-02 2014-10-29 Rhodes Pharmaceuticals Lp IMMEDIATE RELEASE MANIPULATION FORMULATIONS
AR090695A1 (en) 2012-04-18 2014-12-03 Gruenenthal Gmbh PHARMACEUTICAL DOSAGE FORM RESISTANT TO ADULTERATION AND RESISTANT TO IMMEDIATE RELEASE OF DOSE
EP2846835B1 (en) 2012-05-11 2017-09-06 Grünenthal GmbH Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc
US10064945B2 (en) 2012-05-11 2018-09-04 Gruenenthal Gmbh Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc
EP2880011A4 (en) 2012-08-01 2016-03-23 Acura Pharmaceuticals Inc Stabilization of one-pot methamphetamine synthesis systems
WO2014032742A1 (en) 2012-08-27 2014-03-06 Evonik Industries Ag Pharmaceutical or nutraceutical composition with sustained release characteristic and with resistance against the influence of ethanol
ES2625017T3 (en) 2012-08-27 2017-07-18 Evonik Röhm Gmbh Gastro-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
CA2888278A1 (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
EP2968169A1 (en) 2013-03-15 2016-01-20 Mallinckrodt LLC 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
JP6466417B2 (en) 2013-05-29 2019-02-06 グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング A tamper-resistant dosage form with a bimodal release profile
CA2907950A1 (en) 2013-05-29 2014-12-04 Grunenthal Gmbh Tamper-resistant dosage form containing one or more particles
CA2817728A1 (en) 2013-05-31 2014-11-30 Pharmascience Inc. Abuse deterrent immediate release formulation
MX368846B (en) 2013-07-12 2019-10-18 Gruenenthal Gmbh Tamper-resistant dosage form containing ethylene-vinyl acetate polymer.
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
US20150118300A1 (en) 2013-10-31 2015-04-30 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
CA2938699A1 (en) 2014-02-05 2015-08-13 Kashiv Pharma Llc Abuse-resistant drug formulations with built-in overdose protection
WO2015123325A1 (en) 2014-02-12 2015-08-20 Genentech, Inc. Anti-jagged1 antibodies and methods of use
US20160089439A1 (en) 2014-09-28 2016-03-31 Satara Pharmaceuticals, LLC Prevention of Illicit Manufacutre of Methamphetamine from Pseudoephedrine Using Food Flavor Excipients
DK3254059T3 (en) 2015-02-05 2022-02-14 Grey Orange Pte Ltd APPARATUS AND METHOD FOR COMPENSATING A NAVIGATION ROUTE
EP3285745A1 (en) 2015-04-24 2018-02-28 Grünenthal GmbH Tamper-resistant dosage form with immediate release and resistance against solvent extraction
US20170296476A1 (en) 2016-04-15 2017-10-19 Grünenthal GmbH Modified release abuse deterrent dosage forms

Patent Citations (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3865108A (en) * 1971-05-17 1975-02-11 Ortho Pharma Corp Expandable drug delivery device
US3980766A (en) * 1973-08-13 1976-09-14 West Laboratories, Inc. Orally administered drug composition for therapy in the treatment of narcotic drug addiction
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
US4207893A (en) * 1977-08-29 1980-06-17 Alza Corporation Device using hydrophilic polymer for delivering drug to biological environment
US4262017A (en) * 1978-05-22 1981-04-14 Basf Aktiengesellschaft Preparation of a vitamin E dry powder
US4343789A (en) * 1979-07-05 1982-08-10 Yamanouchi Pharmaceutical Co., Ltd. Sustained release pharmaceutical composition of solid medical material
US4427681A (en) * 1982-09-16 1984-01-24 Richardson-Vicks, Inc. Thixotropic compositions easily convertible to pourable liquids
US4603143A (en) * 1983-05-02 1986-07-29 Basf Corporation Free-flowing, high density, fat soluble vitamin powders with improved stability
US4612008A (en) * 1983-05-11 1986-09-16 Alza Corporation Osmotic device with dual thermodynamic activity
US4765989A (en) * 1983-05-11 1988-08-23 Alza Corporation Osmotic device for administering certain drugs
US4783337A (en) * 1983-05-11 1988-11-08 Alza Corporation Osmotic system comprising plurality of members for dispensing drug
US4892889A (en) * 1986-11-18 1990-01-09 Basf Corporation Process for making a spray-dried, directly-compressible vitamin powder comprising unhydrolyzed gelatin
US5556640A (en) * 1991-02-28 1996-09-17 Showa Yakuhin Kako Co., Ltd. Dry gel composition
US5792474A (en) * 1992-05-22 1998-08-11 Goedecke Aktiengesellschaft Process for the production of retarded pharmaceutical compositions
US5601842A (en) * 1993-09-03 1997-02-11 Gruenenthal Gmbh Sustained release drug formulation containing a tramadol salt
US6309668B1 (en) * 1994-02-01 2001-10-30 Aventis Pharma Limited Abuse resistant tablets
US5460826A (en) * 1994-06-27 1995-10-24 Alza Corporation Morphine therapy
US6261599B1 (en) * 1994-11-04 2001-07-17 Euro-Celtique, S.A. Melt-extruded orally administrable opioid formulations
US20040081694A1 (en) * 1994-11-04 2004-04-29 Euro-Celtique, S.A. Melt-extruded orally administrable opioid formulations
US5968925A (en) * 1995-06-23 1999-10-19 Boeters & Bauer Process for continuous sintering of granules
US5811126A (en) * 1995-10-02 1998-09-22 Euro-Celtique, S.A. Controlled release matrix for pharmaceuticals
US6228863B1 (en) * 1997-12-22 2001-05-08 Euro-Celtique S.A. Method of preventing abuse of opioid dosage forms
US6245357B1 (en) * 1998-03-06 2001-06-12 Alza Corporation Extended release dosage form
US6821588B1 (en) * 1998-05-25 2004-11-23 Kalle Gmbh & Co. Kg Film containing starch or starch derivatives and polyester urethanes
US7812169B2 (en) * 2000-11-30 2010-10-12 The Children's Medical Center Corporation Method of synthesis of 4-amino-thalidomide enantiomers
US7776314B2 (en) * 2002-06-17 2010-08-17 Grunenthal Gmbh Abuse-proofed dosage system
US20050191244A1 (en) * 2002-10-25 2005-09-01 Gruenenthal Gmbh Abuse-resistant pharmaceutical dosage form

Cited By (67)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9675610B2 (en) 2002-06-17 2017-06-13 Grünenthal GmbH Abuse-proofed dosage form
US10369109B2 (en) 2002-06-17 2019-08-06 Grünenthal GmbH Abuse-proofed dosage form
US8309060B2 (en) 2003-08-06 2012-11-13 Grunenthal Gmbh Abuse-proofed dosage form
US8114383B2 (en) 2003-08-06 2012-02-14 Gruenenthal Gmbh Abuse-proofed dosage form
US8192722B2 (en) 2003-08-06 2012-06-05 Grunenthal Gmbh Abuse-proof dosage form
US8075872B2 (en) 2003-08-06 2011-12-13 Gruenenthal Gmbh Abuse-proofed dosage form
US10130591B2 (en) 2003-08-06 2018-11-20 Grünenthal GmbH Abuse-proofed 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
US10058548B2 (en) 2003-08-06 2018-08-28 Grünenthal GmbH Abuse-proofed dosage form
US11224576B2 (en) 2003-12-24 2022-01-18 Grünenthal GmbH Process for the production of an abuse-proofed 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
US8323889B2 (en) 2004-07-01 2012-12-04 Gruenenthal Gmbh Process for the production of an abuse-proofed solid dosage form
US10729658B2 (en) 2005-02-04 2020-08-04 Grünenthal GmbH Process for the production of an abuse-proofed dosage form
US10675278B2 (en) 2005-02-04 2020-06-09 Grünenthal GmbH Crush resistant delayed-release 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
US20090052818A1 (en) * 2007-07-10 2009-02-26 Jason Matthew Mitmesser Hybrid bearing
US9750701B2 (en) 2008-01-25 2017-09-05 Grünenthal GmbH Pharmaceutical dosage form
US8383152B2 (en) 2008-01-25 2013-02-26 Gruenenthal Gmbh Pharmaceutical dosage form
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
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
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
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
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
US9925146B2 (en) 2009-07-22 2018-03-27 Grünenthal GmbH Oxidation-stabilized tamper-resistant dosage form
US8597681B2 (en) 2009-12-22 2013-12-03 Mallinckrodt Llc Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans
US9198861B2 (en) 2009-12-22 2015-12-01 Mallinckrodt Llc Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans
US9579285B2 (en) 2010-02-03 2017-02-28 Gruenenthal Gmbh Preparation of a powdery pharmaceutical composition by means of an extruder
US9636303B2 (en) 2010-09-02 2017-05-02 Gruenenthal Gmbh Tamper resistant dosage form comprising an anionic polymer
US10300141B2 (en) 2010-09-02 2019-05-28 Grünenthal GmbH Tamper resistant dosage form comprising inorganic salt
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
US8741885B1 (en) 2011-05-17 2014-06-03 Mallinckrodt Llc Gastric retentive extended release pharmaceutical compositions
US8658631B1 (en) 2011-05-17 2014-02-25 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
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
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
US9468636B2 (en) 2011-05-17 2016-10-18 Mallinckrodt Llc Combination composition comprising oxycodone 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
US10695297B2 (en) 2011-07-29 2020-06-30 Grünenthal GmbH Tamper-resistant tablet providing immediate drug release
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
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
US10064945B2 (en) 2012-05-11 2018-09-04 Gruenenthal Gmbh Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc
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
US9301918B2 (en) 2013-03-15 2016-04-05 Mallinckrodt Llc Abuse deterrent solid dosage form for immediate release with functional score
US11464747B2 (en) 2013-03-15 2022-10-11 R.P. Scherer Technologies, Llc Abuse resistant capsule
US10744097B2 (en) 2013-03-15 2020-08-18 R.P. Scherer Technologies, Llc Abuse resistant capsule
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
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
US11583493B2 (en) 2014-07-03 2023-02-21 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
US11478426B2 (en) 2018-09-25 2022-10-25 SpecGx LLC Abuse deterrent immediate release capsule dosage forms

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US20200375905A1 (en) 2020-12-03
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US20150056147A1 (en) 2015-02-26
US20140093559A1 (en) 2014-04-03

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