CA2520312A1 - Matrix compositions for controlled delivery of drug substances - Google Patents

Matrix compositions for controlled delivery of drug substances Download PDF

Info

Publication number
CA2520312A1
CA2520312A1 CA002520312A CA2520312A CA2520312A1 CA 2520312 A1 CA2520312 A1 CA 2520312A1 CA 002520312 A CA002520312 A CA 002520312A CA 2520312 A CA2520312 A CA 2520312A CA 2520312 A1 CA2520312 A1 CA 2520312A1
Authority
CA
Canada
Prior art keywords
composition according
acid
composition
active substance
daltons
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002520312A
Other languages
French (fr)
Other versions
CA2520312C (en
Inventor
Gina Fischer
Daniel Bar-Shalom
Lillian Slot
Anne-Marie Lademann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Egalet Ltd
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from PCT/DK2003/000765 external-priority patent/WO2004041252A1/en
Application filed by Individual filed Critical Individual
Publication of CA2520312A1 publication Critical patent/CA2520312A1/en
Application granted granted Critical
Publication of CA2520312C publication Critical patent/CA2520312C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0087Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0092Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/2027Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2095Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/28Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806Coating materials
    • A61K9/2833Organic macromolecular compounds
    • A61K9/286Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/28Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2893Tablet coating processes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02Muscle relaxants, e.g. for tetanus or cramps
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives

Abstract

A novel matrix composition for pharmaceutical use. The matrix composition has been designed so that it is especially suitable in those situation where an improved bioavailability is desired and/or in those situation where a slightly or insoluble active substance is employed. Accordingly, a controlled release pharmaceutical composition for oral use is provided in the form of a coated matrix composition, the matrix composition comprising i) a mixture of a first and a second polymer that have plasticizing properties and which have melting points or melting intervals of a temperature of at the most 200~C, the first polymer being selected from the group consisting of polyethylene glycols and polyethylene oxides, and the second polymer being selected form block copolymer of ethylene oxide and propylene oxide including poly(ethylene-glycol-b-(DL-lactic acid-co-glycolic acid) - b-ethylene glycol (PEG-PLGA PEG), poly((DL-lactic acid-co-glycolic acid) - g-ethylene glycol) (PLGA-g-PEG), poloxamers and polyethylene oxide - polypropylene oxide (PEO-PPO), ii) a therapeutically, prophylactically and/or diagnostically active substance, the matrix composition being provided with a coating having at least one opening exposing at one surface of said matrix, wherein the active substance is released with a substantially zero order release.

Claims (69)

1. A controlled release pharmaceutical composition for oral use in the form of a coated matrix composition, the matrix composition comprising i) a mixture of a first and a second polymer that have plasticizing properties and which have melting points or melting intervals of a temperature of at the most 200 °C, the first polymer being selected from the group consisting of polyethylene glycols and polyethylene oxides, and the second polymer being selected from block copolymer of ethylene oxide and propylene oxide including poly(ethylene-glycol-b-(DL-lactic acid-co-glycolic acid)-b-ethylene glycol (PEG-PLGA PEG), poly((DL-lactic acid-co-glycolic acid)-g-ethylene glycol) (PLGA-g-PEG), poloxamers and polyethylene oxide - polypropylene oxide (PEO-PPO), ii) a therapeutically, prophylactically and/or diagnostically active substance, the matrix composition being provided with a coating having at least one opening exposing at one surface of said matrix, the coating comprising i) a first cellulose derivative which has thermoplastic properties and which is substantially insoluble in the aqueous medium in which the composition is to be used, and at least one of ii) a second cellulose derivative which is soluble or dispersible in water, iii) a plasticizer, and iv) a filler, wherein the active substance is released with a substantially zero order release.
2. A composition according to claim 1, wherein the first polymer is a polyethylene glycol and/or a polyethylene oxide having a molecular weight of at least about 20,000 in crystalline and/or amorphous form or a mixture such polymers.
3. A composition according to claim 1 or 2, wherein the polyethylene glycol and/or polyethylene oxide has a molecular weight of from about 20,000 daltons, such as, e.g., from about 20,000 to about 700,000 daltons, from about 20,000 to about 600,000 daltons, from about 35,000 to about 500,000 daltons, from about 35,000 to about 400,000 daltons, from about 35,000 to about 300,000 daltons, from about 50,000 to about 300,000 daltons, such as, e.g. about 35,000 daltons, about 50,000 daltons, about 75,000 daltons, about 100,000 daltons, about 150,000 daltons, about 200,000 daltons, about 250,000 daltons, about 300,000 daltons or about 400,000 daltons.
4. A composition according to claim 3, wherein the polyethylene oxide has a molecular weight of about 35,000 daltons, about 50,000 daltons, about 100,000 daltons, and about 200,000 daltons.
5. A composition according to any of the preceding claims, wherein the first polymer has a melting point of about 20-120 °C such as, e.g. from about 30 to about 100 °C or from about 40 to about 80 °C.
6. A composition according to any of the preceding claims, wherein the concentration of the first polymer in the matrix composition is from about 10 to about 99.5% such as, e.g., from about 20 to about 99%, from about 30 to about 99% w/w, from about 35 to about 95% w/w, from about 35 to about 90% w/w, from about 35 to about 85% w/w, from about 35 to about 80% w/w, from about 40 to about 75% w/w, from about 45 to about 70% w/w, from about 45 to about 65% w/w. from about 55 to about 85% w/w or from about 60 to about 85% w/w.
7. A composition according to any of the preceding claims, wherein the second polymer has a molecular weight of at least about 2,000 daltons.
8. A composition according to any of the preceding claims, wherein the second polymer is a poloxamer that has the formula HO(C2H4O)a(C3H6O)b(C2H4O)a H, and a is an integer from about 10 to about 150 such as, e.g., from about 30 to about 140, from about 50 to about 100, from about 65 to about 90, from about to about 90 and b is an integer from about 10 to about 80 such as, e.g., from about 15 to about 80, from about 20 to about 60, from about 25 to about 55.
9. A composition according to claim 8, wherein the poloxamer has a molecular weight of from about 2,000 daltons to about 20,000 daltons such as, e.g., from about 4,000 daltons to about 15,000 daltons or from about 6,000 daltons to about 10,000 daltons.
10. A composition according to any of the preceding claims, wherein the second polymer has a melting point of about 20-120 °C such as, e.g. from about 30 to about 100 °C or from about 40 to about 80 °C.
11. A composition according to any of the preceding claims, wherein the second polymer has a HLB value of at least about 18 such as, e.g., at least about 20.
12. A composition according to any of the preceding claims, wherein the concentration of the second polymer in the matrix composition is from about 0.5% to about 95% w/w such as, e.g., from about 1% to about 90% w/w, from about 5% w/w to about 90% w/w, from about 10% to about 90% w/w, from about 10% to about 80% w/w, from about 10% to about 70% w/w, from about 10% to about 60%, from about 10% to about 50%, from about 15% to about 50% w/w, from about 10% to about 45% w/w, from about 10% to about 40% w/w, from about 15% to about 40% w/w, from about 15% to about 35% w/w or from about 15% to about 30% w/w.
13. A pharmaceutical composition according to any of the preceding claims for controlled release of the active substance into an aqueous medium by erosion of at least one surface of the composition.
14. A composition according to any of the preceding claims, wherein the active substance is present in any of its crystalline, polymorphous or amorphous forms or mixtures thereof.
15. A pharmaceutical composition according to any of the preceding claims, wherein the active substance at least partially is present in solid form in the dispersion.
16. A pharmaceutical composition according to any of the preceding claims, wherein the active substance at least partially is present in a molecular dispersion such as, e.g., in the form of a solid or semi-solid solution.
17. A pharmaceutical composition according to claim 16, wherein the active substance is present in a molecular dispersion including a solid solution.
18. A pharmaceutical composition according to claim 16, wherein the active substance at least partially is present in a colloidal dispersion.
19. A pharmaceutical composition according to claim 14, wherein the active substance at least partially is present in a crystalline form.
20. A pharmaceutical composition according to any of the preceding claims, wherein the active substance at least partially is present in amorphous form with a mean particle size of from about 0.01 µm to about 500 µm such as, e.g., from about 0.05 µm to about 500 µm, from about 0.1 µm to about 500 µm, typically from about 0.5 µm to about 300 µm, more typically from about 1 µm to about 200 µm, especially from about 1 µm to about 100 µm.
21. A composition according to any of the preceding claims, wherein the first and the second polymer together form a dispersion medium in which the active substance is contained.
22. A composition according to any of the preceding claims comprising a stabilizing agent.
23. A composition according to claim 22, wherein the stabilizing agent is selected from the group consisting of diffusion and dissolution adjusting agents, pH-adjusting agents, buffering agents, agents that does not increase the mobility of the ingredients in the composition, agents that prevent crystal formation and agents that have antioxidative properties.
24. A composition according to claim 22 or 23, wherein the stabilizing agent is selected from the group consisting of inorganic acids, inorganic bases, inorganic salts, organic acids or bases and pharmaceutically acceptable salts thereof, saccharides, oligosaccharides, polysaccharides, and cellulose and cellulose derivatives, or mixtures thereof.
25. A composition according to claim 24, wherein the organic acid is a mono-, di-oligo, polycarboxylic acid or amino acids such as, e.g. acetic acid, ethanoic acid, succinic acid, citric acid, tartaric acid, acrylic acid, benzoic acid, malic acid, maleic acid, adipic acid, angelic acid, ascorbic acid/vitamin C, carbamic acid, cinnamic acid, citramalic acid, formic acid, fumaric acid, gallic acid, gentisic acid, glutaconic acid, glutaric acid, glyceric acid, glycolic acid, glyoxylic acid, lactic acid, levulinic acid, malonic acid, mandelic acid, oxalic acid, oxamic acid, pimelic acid, pyruvic acid, aspartic and glutamic acid, or mixtures thereof.
26. A composition according to claim 24, wherein the inorganic acid is pyrophosphoric, glycerophosphoric, phosphoric such as ortho or meta phosphoric, boric acid, hydrochloric acid, or sulfuric acid, or mixtures thereof.
27. A composition according to claim 24, wherein the suitable inorganic compounds include aluminium.
28. A composition according to claim 24, wherein the suitable organic bases are selected from the group consisting of p-nitrophenol, succinimide, benzenesulfonamide, 2-hydroxy-2cyclohexenone, imidazole, pyrrole, diethanolamine, ethyleneamine, tris (hydroxymethyl) aminomethane, hydroxylamine and derivates of amines, sodium citrate, aniline, and hydrazine, or mixtures thereof.
29. A composition according to claim 24, wherein the suitable inorganic bases are selected from the group consisting of aluminium oxide such as, e.g., aluminium oxide trihydrate, alumina, sodium hydroxide, potassium hydroxide, calcium carbonate, ammonium carbonate, ammnonium hydroxide, KOH and the like, or mixtures thereof.
30. A composition according to claim 24, wherein the pharmaceutically acceptable salt of an organic acid is e.g. an alkali metal salt or an alkaline earth metal salt such as, e.g. sodium phosphate, sodium dihydrogenphosphate, disodium hydrogenphosphate etc., potassium phosphate, potassium dihydrogenphosphate, potassium hydrogenphosphate etc., calcium phosphate, dicalcium phosphate etc., sodium sulfate, potassium sulfate, calcium sulfate, sodium carbonate, sodium hydrogencarbonate, potassium carbonate, potassium hydrogencarbonate, calcium carbonate, magnesium carbonate etc., sodium acetate, potassium acetate, calcium acetate, sodium succinate, potassium succinate, calcium succinate, sodium citrate, potassium citrate, calcium citrate, sodium tartrate, potassium tartrate, calcium tartrate, zinc gluconate, zinc sulphate etc., or mixtures thereof.
31. A composition according to claim 24, wherein the inorganic salt is sodium chloride, potassium chloride, calcium chloride, magnesium chloride etc., or mixtures thereof.
32. A composition according to claim 24, wherein the pharmaceutically acceptable excipient is selected from glucose and other monosaccharides, ribose, arabinose, xylose, lyxose, allose, altrose, inosito, glucose, sorbitol, mannose, gulose, idose, galactose, talose, mannitol, fructose, lactose, sucrose, and other disaccharides, dextrin, dextran or other polysaccharides, amylose, xylan, cellulose and cellulose derivatives such as, e.g. microcrystalline cellulose, methyl cellulose, ethyl cellulose, ethylhydroxyethyl cellulose, ethylmethylcellulose, hydroxyethylcellulose, hydroxyethylmethyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, hydroxymethylpropyl cellulose, hydroxypropylmethyl cellulose, amylopectin, pectin, starch, sodium starch etc.,kaolin, bentonit, acacia, alginic acid, sodium alginate, calcium alginate, gelatin, dextrose, molasses, extract of Irish moss, panwar gum, ghatti gum, mucilage of isapol husk, veegum, glycollate, magnesium stearate, calcium stearate, stearic acid, talc, titanium dioxide, silicium dioxide, clays, croscarmellose, gums, agar etc., or mixtures thereof.
33. A composition according to any of the preceding claims further comprising a pharmaceutically acceptable excipient selected from the group consisting of fillers, diluents, disintegrants, glidants, pH-adjusting agents, viscosity adjusting agents, solubility increasing or decreasing agents, osmotically active agents and solvents.
34. A composition according to claim 24, wherein the stabilizing agent is citric acid including solvates and anhydrates thereof.
35. A composition according to claim 34, wherein the citric acid has a water content of at the most about 15% w/w such as, e.g., at the most about 12% w/w, such as e.g., at the most about 10% w/w, such as e.g., at the most about 8%
w/w, such as e.g., at the most about 5% w/w, such as e.g., at the most about 3%
w/w, such as e.g., at the most about 2% w/w, such as at the most about 1 % w/w or at the most about 0.5% w/w.
36. A composition according to claim 24, wherein the stabilizing agent is a phosphoric acid or a phosphonic acid or a salt thereof.
37. A composition according to claim 36, wherein the phosphoric acid is ortho or meta phoshoric acid or a mixture thereof.
38. A composition according to any of the preceding claims, wherein the concentration of the active substance in the composition corresponds to a concentration of at the most the saturated concentration in component i) at a temperature corresponding to the melting point or the lowest end point of the melting interval of component i).
39. A composition according to any of the preceding claims, wherein the first polymer and/or the second polymer is of a quality that ensures that free radicals formed, if any, do not significantly increase the degradation of the active substance in the composition.
40. A composition according to any of the preceding claims further comprising one or more antioxidants that inhibits the formation of peroxides and/or inactivates any peroxides present.
41. A composition according to any of the preceding claims, wherein the active substance has antioxidant properties.
42. A composition according to any of the preceding claims, wherein the composition is stable with respect to physical stability.
43. A composition according to any of the preceding claims, wherein the composition is stable with respect to in vitro dissolution of the active substance from the composition.
44. A composition according to claim 43, wherein the composition is stable with respect to in vitro dissolution behaviour in such a manner that t50%, i.e. the time for 50% w/w of the active substance to dissolve in a dissolution medium, differs at the most ~ 20% w/w such as, e.g., at the most ~ 15% w/w, at the most ~ 10%
w/w, at the most ~ 7.5% w/w, at the most ~ 5% w/w, at the most ~ 2.5% w/w, at the most ~ 1.5% w/w or at the most 1% w/w when two compositions from the same batch is compared with a time difference of 2 weeks under similar storage and test conditions.
45. A composition according to any of the preceding claims, wherein the composition is stable with respect to chemical stability of the active substance.
46. A composition according to claim 45, wherein the concentration of the active substance in the composition decreases at the most 20% w/w such as, e.g. at the most 15% w/w, at the most 10% w/w, at the most 7.5% w/w or at the most 5% w/w when stored at room temperature for a time period of at least 3 months such as, e.g. 6 months, 12 months, 18 months or 24 months and a relative humidity of at the most 75% such as, e.g., at the most 70%, at the most 65%, at the most 60%, at the most 55%, at the most 50% or at the most 45%.
47. A composition according to any of the preceding claims, wherein the active substance is present in the composition in a concentration of from about 0.1 to about 98% w/w such as, e.g. at the most about 90% w/w, at the most about 85%
w/w, at the most about 80% w/w, at the most about 75% w/w, at the most about 70% w/w, at the most about 65% w/w or at the most about 60% w/w.
48. A composition according to any of the preceding claims, wherein the active substance has a solubility of at the most about 3 mg/ml such as, e.g., at the most about 1 mg/ml, at the most about 0.1 mg/ml, at the most about 0.05 mg/ml such as, e.g. at the most about 0.001 mg/ml in water at ambient temperature.
49. A composition according to any of the preceding claims, wherein any exposed matrix surfaces erode at a substantially constant rate.
50. A composition according to any of the preceding claims, wherein in the aqueous medium in which the composition is to be used, the coating does not completely crumble or erode before the matrix has completely eroded.
51. A composition according to any of the preceding claims, wherein said first cellulose derivative is a cellulose ether which, when heated, is shapeable by molding or extrusion, including injection molding, blow molding and compression molding.
52. A composition according to claim 51 in which the cellulose ether comprises at least one ethylcellulose.
53. A composition according to any of claims 1-51 in which said first cellulose derivative is selected from the group consisting of cellulose acetate, cellulose propionate and cellulose nitrate.
54. A composition according to any of the preceding claims in which said second cellulose derivative is selected from the group consisting of methylcellulose, carboxymethylcellulose and salts thereof, cellulose acetate phthalate, microcrystalline cellulose, ethylhydroxyethylcellulose, ethylmethylcellulose, hydroxyethylcellylose, hydroxyethylmethylcellulose, hydroxypropylcellulose, hydroxymethylcellulose and hydroxymethylpropylcellulose.
55. A composition according to claim 54 in which said salt of carboxymethylcelllulose is selected from the group consisting of alkali metal and alkaline earth metal salts.
56. A composition according to any of the preceding claims, in which said plasticizer is selected from the group consisting of phosphate esters;
phthalate esters; amides; mineral oils; fatty acids and esters thereof with polyethylene glycol, glycerin or sugars; fatty alcohols and ethers thereof with polyethylene glycol, glycerin or sugars; vegetable oils and hydrogenated vegetable oils;

nitrobenzene, carbon disulfide, .beta.-naphtyl salicylate, phthalyl glycolate, diocyl phthalate etc.
57. A composition according to claim 56 in which said fatty alcohol is selected from the group consisting of cetostearyl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol and myristyl alcohol.
58. A composition according to any of claims 1-55 in which said plasticizer is a non-ionic surfactant.
59. A composition according to any of the preceding claims, wherein the solid dispersion does not contain polyethylene glycol 2000 monostearate or polyethylene glycol 400 monostearate.
60. A composition according to any of the preceding claims, wherein the first polymer has a molecular weight of at least 100,000 daltons and at the most 400,000 daltons.
61. A composition according to any of the preceding claims, wherein the release of the active substance from the composition is zero order and about 50% w/w of the active substance is released from the composition within 5-6 hours from start of release as measured by the dissolution test described herein.
62. A composition according to any of claims 1-60, wherein the release of the active substance from the composition is zero order and about 50% w/w of the active substance is released from the composition within 4-5 hours from start of release as measured by the dissolution test described herein.
63. A composition according to any of claims 1-60, wherein the release of the active substance from the composition is zero order and about 50% w/w of the active substance is released from the composition within 3-4 hours from start of release as measured by the dissolution test described herein.
64. A composition according to any of claims 1- 60, wherein the release of the active substance from the composition is zero order and about 50% w/w of the active substance is released from the composition Within 2-3 hours from start of release as measured by the dissolution test described herein.
65. A composition according to any of the preceding claims, wherein the release of the active substance from the composition is substantially delayed for 0.25 to 4 hours, e.g. for 0.5 to 3 hours, such as from 1 to 2 hours before the zero order release starts as measured by the dissolution test described herein.
66. A method for preparing a composition according to any of claims 1-65, the method comprises injection moulding of a melted or semi-solid mixture of the individual components making up the composition into a suitable form, application of a coating by means of injection moulding and cooling the thus prepared coated composition to solidify the composition.
67. A method according to claim 66, wherein the method is a substantially single continuous process.
68. A method according to claim 67, Wherein the cooling is performed under controlled conditions to a temperature of from about 0 °C to about 20 °C such as, e.g. from about 5 °C to about 18 °C, from about 10 °C to about 16 °C such as, e.g. about 10 °C, about 12 °C, about 14 °C, about 15 °C or about 16 °C.
69. A method according to claim 66 or 67 comprising a step of heating while the polymer and the active substance is in physical contact with each other.
CA2520312A 2003-03-26 2004-03-26 Matrix compositions for controlled delivery of drug substances Expired - Fee Related CA2520312C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
DKPA200300464 2003-03-26
DKPA200300464 2003-03-26
PCT/DK2003/000765 WO2004041252A1 (en) 2002-11-08 2003-11-07 Controlled release carvedilol compositions
DKPCT/DK03/00765 2003-11-07
PCT/DK2004/000217 WO2004084869A1 (en) 2003-03-26 2004-03-26 Matrix compositions for controlled delivery of drug substances

Publications (2)

Publication Number Publication Date
CA2520312A1 true CA2520312A1 (en) 2004-10-07
CA2520312C CA2520312C (en) 2013-06-18

Family

ID=33099580

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2520312A Expired - Fee Related CA2520312C (en) 2003-03-26 2004-03-26 Matrix compositions for controlled delivery of drug substances

Country Status (9)

Country Link
US (2) US8298581B2 (en)
EP (3) EP2186510B1 (en)
JP (1) JP4989217B2 (en)
AT (2) ATE454886T1 (en)
CA (1) CA2520312C (en)
DE (2) DE602004014747D1 (en)
DK (1) DK1610768T3 (en)
ES (1) ES2307003T3 (en)
WO (1) WO2004084869A1 (en)

Families Citing this family (95)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU3024399A (en) * 1998-04-03 1999-10-25 Bm Research A/S Controlled release composition
DE10026698A1 (en) * 2000-05-30 2001-12-06 Basf Ag Self-emulsifying active ingredient formulation and use of this formulation
EP1429744A1 (en) 2001-09-21 2004-06-23 Egalet A/S Morphine polymer release system
US20040234602A1 (en) * 2001-09-21 2004-11-25 Gina Fischer Polymer release system
US7776314B2 (en) 2002-06-17 2010-08-17 Grunenthal Gmbh Abuse-proofed dosage system
US20040151772A1 (en) * 2002-11-08 2004-08-05 Egalet A/S Controlled release carvedilol compositions
DE602004031096D1 (en) * 2003-03-26 2011-03-03 Egalet As MORPHINE SYSTEM WITH CONTROLLED RELEASE
US8298581B2 (en) * 2003-03-26 2012-10-30 Egalet A/S Matrix compositions for controlled delivery of drug substances
DE102004032051A1 (en) 2004-07-01 2006-01-19 Grünenthal GmbH Process for the preparation of a secured against misuse, solid dosage form
DE10361596A1 (en) 2003-12-24 2005-09-29 Grünenthal GmbH Process for producing an anti-abuse dosage form
DE102005005446A1 (en) 2005-02-04 2006-08-10 Grünenthal GmbH Break-resistant dosage forms with sustained release
US8075872B2 (en) 2003-08-06 2011-12-13 Gruenenthal Gmbh Abuse-proofed dosage form
US20070048228A1 (en) 2003-08-06 2007-03-01 Elisabeth Arkenau-Maric Abuse-proofed dosage form
DE10336400A1 (en) 2003-08-06 2005-03-24 Grünenthal GmbH Anti-abuse dosage form
US8025899B2 (en) 2003-08-28 2011-09-27 Abbott Laboratories Solid pharmaceutical dosage form
US8377952B2 (en) * 2003-08-28 2013-02-19 Abbott Laboratories Solid pharmaceutical dosage formulation
US7201920B2 (en) 2003-11-26 2007-04-10 Acura Pharmaceuticals, Inc. Methods and compositions for deterring abuse of opioid containing dosage forms
DE102004032049A1 (en) 2004-07-01 2006-01-19 Grünenthal GmbH Anti-abuse, oral dosage form
DE102005005449A1 (en) 2005-02-04 2006-08-10 Grünenthal GmbH Process for producing an anti-abuse dosage form
US20060252831A1 (en) * 2005-05-06 2006-11-09 Christopher Offen Method for the treatment of magnesium and potassium deficiencies
US20060252830A1 (en) * 2005-05-06 2006-11-09 Brandon Stephen F Method for the treatment of magnesium and potassium deficiencies
JP5161075B2 (en) * 2005-06-03 2013-03-13 エガレット エイ/エス Solid pharmaceutical composition having a first fraction of a dispersion medium and a second fraction of a matrix, wherein the second fraction is first at least partially exposed to gastrointestinal fluid
US9198865B2 (en) * 2006-01-19 2015-12-01 Dow Global Technologies Llc Biologically active composition comprising ethylcellulose
WO2008086804A2 (en) * 2007-01-16 2008-07-24 Egalet A/S Use of i) a polyglycol and n) 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
DE102007011485A1 (en) 2007-03-07 2008-09-11 Grünenthal GmbH Dosage form with more difficult abuse
KR100932613B1 (en) * 2007-04-27 2009-12-17 한남대학교 산학협력단 Preparation of nanospheres composed of biocompatible polymers using polymer melt process for drug delivery and nanospheres thereof
EP2155167A2 (en) 2007-06-04 2010-02-24 Egalet A/S Controlled release pharmaceutical compositions for prolonged effect
US7940978B2 (en) * 2007-06-05 2011-05-10 General Electric Company Automatic characterization of cellular motion
CN101557802B (en) * 2007-12-03 2013-10-30 特里逻辑药业有限责任公司 Self solidifying bioerodible barrier implant
RU2493830C2 (en) 2008-01-25 2013-09-27 Грюненталь Гмбх Drug form
CN102014973A (en) 2008-02-29 2011-04-13 弗罗桑医疗设备公司 Device for promotion of hemostasis and/or wound healing
BRPI0912014A2 (en) 2008-05-09 2019-03-06 Grünenthal GmbH A process for preparing an intermediate powder formulation and a final solid dosage form using a spray freeze step
AU2009258120B2 (en) * 2008-06-10 2014-11-27 Teva Pharmaceutical Industries, Ltd. Rasagiline soft gelatin capsules
CN104997732A (en) 2008-06-16 2015-10-28 佰恩德治疗股份有限公司 Drug loaded polymeric nanoparticle and method of making and using same
WO2010005726A2 (en) 2008-06-16 2010-01-14 Bind Biosciences Inc. Therapeutic polymeric nanoparticles with mtor inhibitors and methods of making and using same
EP2309991B1 (en) 2008-06-16 2019-03-06 Pfizer Inc Therapeutic polymeric nanoparticles comprising vinca alkaloids and methods of making and using same
WO2010033832A2 (en) * 2008-09-19 2010-03-25 Evestra, Inc. Estriol formulations
WO2010068866A2 (en) 2008-12-12 2010-06-17 Bind Biosciences Therapeutic particles suitable for parenteral administration and methods of making and using same
JP2012512175A (en) 2008-12-15 2012-05-31 バインド バイオサイエンシズ インコーポレイテッド Long-circulating nanoparticles for sustained release of therapeutic agents
NZ594208A (en) 2009-02-06 2012-10-26 Egalet Ltd Pharmaceutical compositions resistant to abuse
WO2010089132A1 (en) 2009-02-06 2010-08-12 Egalet A/S Immediate release composition resistant to abuse by intake of alcohol
WO2010149169A2 (en) 2009-06-24 2010-12-29 Egalet A/S Controlled release formulations
JP2012533585A (en) 2009-07-22 2012-12-27 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 dosage forms for oxidation-sensitive opioids
BR112012001547A2 (en) 2009-07-22 2016-03-08 Gruenenthal Gmbh hot melt extruded pharmaceutical dosage form
EP3064064A1 (en) 2009-09-30 2016-09-07 Acura Pharmaceuticals, Inc. Methods and compositions for deterring abuse
EP2509634B1 (en) 2009-12-11 2019-03-06 Pfizer Inc Stable formulations for lyophilizing therapeutic particles
EP2515942B1 (en) 2009-12-15 2020-02-12 Pfizer Inc. Therapeutic polymeric nanoparticle compositions with high glass transition temperature or high molecular weight copolymers
EP2547371A1 (en) 2010-03-15 2013-01-23 Ferrosan Medical Devices A/S A method for promotion of hemostasis and/or wound healing
US10039709B2 (en) 2010-06-04 2018-08-07 Trilogic Pharma Llc Bioadhesive compositions for epithelial drug delivery
WO2012028319A1 (en) 2010-09-02 2012-03-08 Grünenthal GmbH Tamper resistant dosage form comprising inorganic salt
WO2012028318A1 (en) 2010-09-02 2012-03-08 Grünenthal GmbH Tamper resistant dosage form comprising an anionic polymer
EP2629760A4 (en) * 2010-10-22 2014-04-02 Bind Therapeutics Inc Therapeutic nanoparticles with high molecular weight copolymers
KR101775727B1 (en) 2010-12-15 2017-09-19 가톨릭대학교 산학협력단 Polyalkylenglycol-linker-polyester copolymer, method preparing the same and usage thereof
BR112014002022A2 (en) 2011-07-29 2017-02-21 Gruenenthal Gmbh tamper-resistant tablet providing immediate drug release
CN103857386A (en) 2011-07-29 2014-06-11 格吕伦塔尔有限公司 Tamper-resistant tablet providing immediate drug release
TWI641396B (en) 2011-09-23 2018-11-21 Bvw控股公司 Medical copolymer
US20130225625A1 (en) * 2012-02-28 2013-08-29 Grunenthal Gmbh Tamper-resistant pharmaceutical dosage form comprising nonionic surfactant
US20130225697A1 (en) 2012-02-28 2013-08-29 Grunenthal Gmbh Tamper-resistant dosage form comprising pharmacologically active compound and anionic polymer
CA2865349C (en) 2012-03-06 2021-07-06 Ferrosan Medical Devices A/S Pressurized container containing haemostatic paste
AU2013248351B2 (en) 2012-04-18 2018-04-26 Grunenthal Gmbh Tamper resistant and dose-dumping resistant pharmaceutical dosage form
KR101455901B1 (en) * 2012-05-04 2014-11-03 성균관대학교산학협력단 Eutectic composition comprising celecoxib and poloxamer
US10064945B2 (en) 2012-05-11 2018-09-04 Gruenenthal Gmbh Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc
CA2874290C (en) 2012-06-12 2020-02-25 Ferrosan Medical Devices A/S Dry haemostatic composition
KR20150059167A (en) 2012-07-06 2015-05-29 에갈렛 리미티드 Abuse deterrent pharmaceutical compositions for controlled release
CA2885193C (en) 2012-09-17 2021-04-27 Bind Therapeutics, Inc. Process for preparing therapeutic nanoparticles
MX366159B (en) 2012-11-30 2019-07-01 Acura Pharmaceuticals Inc Self-regulated release of active pharmaceutical ingredient.
BR112015026549A2 (en) 2013-05-29 2017-07-25 Gruenenthal Gmbh tamper-proof dosage form containing one or more particles
MX2015016254A (en) 2013-05-29 2016-04-20 Gruenenthal Gmbh Tamper resistant dosage form with bimodal release profile.
CA2912357C (en) 2013-06-21 2019-12-31 Ferrosan Medical Devices A/S Vacuum expanded dry composition and syringe for retaining same
AU2014289187B2 (en) 2013-07-12 2019-07-11 Grunenthal Gmbh Tamper-resistant dosage form containing ethylene-vinyl acetate polymer
EP3052084A1 (en) * 2013-09-30 2016-08-10 Universiteit Gent Polyurethanes as oral drug delivery platform
US10350232B1 (en) 2013-11-04 2019-07-16 Peter D. Jaillet Medicinal drops
CA2931553C (en) 2013-11-26 2022-01-18 Grunenthal Gmbh Preparation of a powdery pharmaceutical composition by means of cryo-milling
RU2678592C1 (en) 2013-12-11 2019-01-30 Ферросан Медикал Дивайсиз А/С Dry composition comprising extrusion enhancer
WO2015091352A1 (en) 2013-12-16 2015-06-25 Grünenthal GmbH Tamper resistant dosage form with bimodal release profile manufactured by co-extrusion
MX2016012009A (en) 2014-03-14 2016-12-05 Pfizer Therapeutic nanoparticles comprising a therapeutic agent and methods of making and using same.
WO2015145459A1 (en) 2014-03-26 2015-10-01 Sun Pharma Advanced Research Company Ltd. Abuse deterrent immediate release coated reservoir solid dosage form
MX2016014738A (en) 2014-05-12 2017-03-06 Gruenenthal Gmbh Tamper resistant immediate release capsule formulation comprising tapentadol.
WO2015181059A1 (en) 2014-05-26 2015-12-03 Grünenthal GmbH Multiparticles safeguarded against ethanolic dose-dumping
JP6726852B2 (en) 2014-10-13 2020-07-22 フェッローサン メディカル ディバイス エー/エス Dry composition for use in hemostasis and wound healing
AU2015371184B2 (en) 2014-12-24 2020-06-25 Ferrosan Medical Devices A/S Syringe for retaining and mixing first and second substances
US10182993B2 (en) * 2015-04-06 2019-01-22 Patheon Softgels Inc. Compositions for colonic delivery of drugs
US10611894B2 (en) * 2015-04-07 2020-04-07 Mitsubishi Chemical Corporation Resin composition and multilayer structure using same, and method of improving long-run stability
AU2016251854A1 (en) 2015-04-24 2017-10-19 Grunenthal Gmbh Tamper-resistant dosage form with immediate release and resistance against solvent extraction
US20180177718A1 (en) * 2015-05-29 2018-06-28 Envisia Therapeutics, Inc. Implant for treatment of an ocular condition
CA2986981A1 (en) 2015-07-03 2017-01-12 Ferrosan Medical Devices A/S Syringe for mixing two components and for retaining a vacuum in a storage condition
EP3135272A1 (en) * 2015-08-31 2017-03-01 Basf S.A. Compositions for mouth wash in the form of tablets
US11103581B2 (en) 2015-08-31 2021-08-31 Acura Pharmaceuticals, Inc. Methods and compositions for self-regulated release of active pharmaceutical ingredient
JP2018526414A (en) 2015-09-10 2018-09-13 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 Protection against oral overdose with abuse-inhibiting immediate release formulations
CN108348466A (en) * 2015-12-08 2018-07-31 陶氏环球技术有限责任公司 Include the composition of cellulose ether and soluble ester cellulose ether
EP3184104B1 (en) * 2015-12-23 2018-09-12 Hexal AG Pharmaceutical composition of vortioxetine hydrobromide comprising vortioxetine hydrobromide in a polyethylene oxide matrix
MX2020011866A (en) 2018-05-09 2021-01-20 Ferrosan Medical Devices As Method for preparing a haemostatic composition.
WO2020006408A1 (en) 2018-06-29 2020-01-02 Incyte Corporation Formulations of an axl/mer inhibitor
KR102538853B1 (en) * 2019-10-30 2023-06-01 주식회사 에이디 Pheromone Dispenser using Halloysite pellet as pheromone-absorbing material and producing method thereof
CN114796135B (en) * 2022-03-29 2023-04-07 海南久常制药有限公司 Sucralfate oral preparation and preparation method thereof

Family Cites Families (60)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1018456A (en) 1972-06-26 1977-10-04 Hans Lowey Prolonged release lozenges
JPS5518694B2 (en) 1973-04-02 1980-05-21
US4330338A (en) 1978-10-02 1982-05-18 Purdue Research Foundation Pharmaceutical coating composition, and preparation and dosages so coated
US4389393A (en) 1982-03-26 1983-06-21 Forest Laboratories, Inc. Sustained release therapeutic compositions based on high molecular weight hydroxypropylmethylcellulose
DE3320583A1 (en) 1983-06-08 1984-12-13 Dr. Karl Thomae Gmbh, 7950 Biberach NEW GALENIC PREPARATION FORMS OF ORAL ANTIDIABETICS AND METHOD FOR THE PRODUCTION THEREOF
AU591171B2 (en) 1983-11-02 1989-11-30 Alza Corporation Dispenser for delivering thermo-responsive composition
US4844984A (en) 1984-03-19 1989-07-04 Alza Corporation Dispensing system with means for increasing delivery of beneficial agent from the system
JPH0246008B2 (en) 1984-06-01 1990-10-12 Takada Seiyaku Kk NIFUEJIPINJIZOKUSEISEIZAINOSEIZOHOHO
US5082655A (en) * 1984-07-23 1992-01-21 Zetachron, Inc. Pharmaceutical composition for drugs subject to supercooling
GB2170104A (en) 1985-01-30 1986-07-30 Warner Lambert Co Coated pharmaceutical dosage forms
IE59066B1 (en) 1985-02-19 1993-12-15 Key Pharma Controlled release potassium chloride
US4892742A (en) 1985-11-18 1990-01-09 Hoffmann-La Roche Inc. Controlled release compositions with zero order release
US4824675A (en) * 1987-07-13 1989-04-25 Alza Corporation Dispenser with movable matrix comprising a plurality of tiny pills
EP0406315B1 (en) * 1988-03-24 1992-11-11 Bukh Meditec A/S Controlled release composition
FI101344B1 (en) 1988-03-31 1998-06-15 Tanabe Seiyaku Co Process for the preparation of a composition for controlled release of a pharmaceutically active substance
JPH04503058A (en) 1989-01-30 1992-06-04 アルザ コーポレイション Dosage form for calcium antagonist administration
DK469989D0 (en) 1989-09-22 1989-09-22 Bukh Meditec PHARMACEUTICAL PREPARATION
IT1237904B (en) 1989-12-14 1993-06-18 Ubaldo Conte CONTROLLED SPEED RELEASE TABS OF ACTIVE SUBSTANCES
US5102668A (en) 1990-10-05 1992-04-07 Kingaform Technology, Inc. Sustained release pharmaceutical preparation using diffusion barriers whose permeabilities change in response to changing pH
GB9025372D0 (en) 1990-11-22 1991-01-09 Nat Res Dev Pharmaceutical dosage forms
US5478577A (en) * 1993-11-23 1995-12-26 Euroceltique, S.A. Method of treating pain by administering 24 hour oral opioid formulations exhibiting rapid rate of initial rise of plasma drug level
US5881926A (en) 1993-03-11 1999-03-16 Taro Pharmaceutical Industries, Ltd. Pharmaceutical compositions in semisolid form and a device for administration thereof
US5656291A (en) * 1994-03-16 1997-08-12 Pharmacia & Upjohn Aktiebolag Controlled release preparation
JPH07100191A (en) 1993-10-06 1995-04-18 Daikyo Yakuhin Kogyo Kk Sustained release suppository
US5419917A (en) 1994-02-14 1995-05-30 Andrx Pharmaceuticals, Inc. Controlled release hydrogel formulation
EP0746310B1 (en) * 1994-02-23 1998-11-18 BM Research A/S Controlled release composition
IL139728A (en) 1995-01-09 2003-06-24 Penwest Pharmaceuticals Compan Aqueous slurry composition containing microcrystalline cellulose for preparing a pharmaceutical excipient
JP3161278B2 (en) 1995-04-26 2001-04-25 株式会社村田製作所 Dielectric porcelain composition
EP0908181B8 (en) 1996-05-20 2009-04-15 Otsuka Pharmaceutical Co., Ltd. Remedy for rosacea
JP2000516222A (en) 1996-08-15 2000-12-05 ロザン ファルマ ゲゼルシャフトミットベシュレンクテル ハフツング Oral pharmaceutical composition that is easy to swallow
US20020054911A1 (en) 2000-05-11 2002-05-09 Boehringer Mannheim Pharmaceutical Corporation-Sm Ithkline Beckman Corporation, Limited Partnershi Novel oral dosage form for carvedilol
US6245357B1 (en) 1998-03-06 2001-06-12 Alza Corporation Extended release dosage form
AU3024399A (en) * 1998-04-03 1999-10-25 Bm Research A/S Controlled release composition
CA2328614C (en) * 1999-02-12 2012-06-26 Biostream, Inc. Matrices for drug delivery and methods for making and using the same
US6267985B1 (en) * 1999-06-30 2001-07-31 Lipocine Inc. Clear oil-containing pharmaceutical compositions
US6562375B1 (en) 1999-08-04 2003-05-13 Yamanouchi Pharmaceuticals, Co., Ltd. Stable pharmaceutical composition for oral use
US6534085B1 (en) * 1999-09-23 2003-03-18 Bioresponse L.L.C. Phytochemicals for promoting weight loss
JP4310010B2 (en) * 1999-10-08 2009-08-05 パナソニック株式会社 Unit battery
EP1233768A1 (en) 1999-11-15 2002-08-28 Smithkline Beecham Carvedilol methanesulfonate
US6352721B1 (en) 2000-01-14 2002-03-05 Osmotica Corp. Combined diffusion/osmotic pumping drug delivery system
US6491949B2 (en) 2000-01-14 2002-12-10 Osmotica Corp. Osmotic device within an osmotic device
US6378165B1 (en) * 2000-02-17 2002-04-30 Emerson Electric Co. Pull handle with interlocking mounting mechanism for wet/dry vacuum appliance
US20010036959A1 (en) * 2000-04-03 2001-11-01 Gabel Rolf Dieter Carvedilol-hydrophilic solutions
US6488962B1 (en) 2000-06-20 2002-12-03 Depomed, Inc. Tablet shapes to enhance gastric retention of swellable controlled-release oral dosage forms
JP2004518734A (en) 2000-10-24 2004-06-24 スミスクライン・ビーチャム・コーポレイション A new formulation of carvedilol
IN191028B (en) 2001-05-17 2003-09-13 Sun Pharmaceutical Ind Ltd
DE10131272B4 (en) * 2001-06-28 2006-03-30 Koenig & Bauer Ag turning device
EP1429744A1 (en) * 2001-09-21 2004-06-23 Egalet A/S Morphine polymer release system
US20040234602A1 (en) 2001-09-21 2004-11-25 Gina Fischer Polymer release system
EP1929998A3 (en) 2001-09-21 2008-11-26 Egalet A/S Controlled release solid dispersions of carvedilol
EP1438028A1 (en) * 2001-09-28 2004-07-21 McNEIL-PPC, INC. Modified release dosage forms
PT1485078E (en) * 2002-03-15 2013-01-14 Cypress Bioscience Inc Milnacipran for the treatment of irritable bowel syndrome
AU2003256848A1 (en) * 2002-07-29 2004-02-16 Alza Corporation Formulations and dosage forms for controlled delivery of topiramate
US20040151772A1 (en) * 2002-11-08 2004-08-05 Egalet A/S Controlled release carvedilol compositions
DE602004031096D1 (en) * 2003-03-26 2011-03-03 Egalet As MORPHINE SYSTEM WITH CONTROLLED RELEASE
US8298581B2 (en) * 2003-03-26 2012-10-30 Egalet A/S Matrix compositions for controlled delivery of drug substances
WO2005007074A2 (en) 2003-07-21 2005-01-27 Bio-Dar Ltd. Gellan gum based oral controlled release dosage forms- a novel platform technology for gastric retention
US8389008B2 (en) 2003-09-19 2013-03-05 Penwest Pharmaceuticals Co. Delayed release dosage forms
US20050163837A1 (en) 2003-12-31 2005-07-28 Garth Boehm Rosiglitazone formulations
JP5161075B2 (en) 2005-06-03 2013-03-13 エガレット エイ/エス Solid pharmaceutical composition having a first fraction of a dispersion medium and a second fraction of a matrix, wherein the second fraction is first at least partially exposed to gastrointestinal fluid

Also Published As

Publication number Publication date
DE602004025159D1 (en) 2010-03-04
US8298581B2 (en) 2012-10-30
EP2186510A2 (en) 2010-05-19
US20100166866A1 (en) 2010-07-01
ATE399538T1 (en) 2008-07-15
US20070042044A1 (en) 2007-02-22
DK1610768T3 (en) 2008-09-22
EP1974726A3 (en) 2008-11-05
ES2307003T3 (en) 2008-11-16
EP1974726B1 (en) 2010-01-13
EP1974726A2 (en) 2008-10-01
WO2004084869A1 (en) 2004-10-07
ATE454886T1 (en) 2010-01-15
EP1610768A1 (en) 2006-01-04
EP2186510B1 (en) 2013-07-10
JP2006521301A (en) 2006-09-21
JP4989217B2 (en) 2012-08-01
EP2186510A3 (en) 2010-06-09
DE602004014747D1 (en) 2008-08-14
EP1610768B1 (en) 2008-07-02
CA2520312C (en) 2013-06-18

Similar Documents

Publication Publication Date Title
CA2520312A1 (en) Matrix compositions for controlled delivery of drug substances
EP3417861B1 (en) Pharmaceutical composition containing jak kinase inhibitor or pharmaceutically acceptable salt thereof
EP2099431B1 (en) Stabilized solid pharmaceutical composition of candesartan cilexetil
US20120309740A1 (en) Pharmaceutical Compositions Having Improved Dissolution Profiles For Poorly Soluble Drugs
EP3785698B1 (en) Edaravone pharmaceutical composition
US11000594B2 (en) Composition comprising an organic liquid diluent and a cellulose ether of very low viscosity
US20150320869A1 (en) Composition comprising an organic liquid diluent and a specific hydroxypropyl methylcellulose
US8962018B2 (en) Oral formulation of anhydrous olanzapine form I
KR20050039732A (en) Method for the formation of ibuprofen crystals
EA031607B1 (en) Pharmaceutical composition
WO2011078821A1 (en) Effervescent tablet and granule formulation comprising cefixime
EP2515850B1 (en) Pharmaceutical compositions comprising cefdinir as an active agent
WO2013109227A1 (en) Pharmaceutical compositions comprising ceftibuten
WO2014095818A1 (en) Formulation comprising amorphous agomelatine
US7105178B2 (en) Cardiotonic composition
US11426351B2 (en) Process for producing a pharmaceutical composition containing micro particles
WO2023080855A1 (en) Pharmaceutical composition comprising mirabegron and calcium salts
EP4285893A1 (en) A combination comprising empagliflozin and metformin hydrochloride
WO2013109202A2 (en) Pharmaceutical compounds comprising cefetamet
KR20210112240A (en) Controlled-released dosage form comprising mirabegron as an active ingredient
EP2671571A1 (en) Controlled-release formulations of clarithromycin
KR20200074046A (en) A pharmaceutical composition for preparing solid dispersion comprising tolvaptan and method for preparing the same
WO2018219801A1 (en) Immediate-release extrudates
EP2813216A1 (en) Stabilized amorphous ticagrelor
KR20160095342A (en) Pharmaceutical composition comprising ecabet or pharmaceutically acceptable salts thereof as an active ingredient

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed

Effective date: 20190326