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Paramétrages

Paramétrages

1. WO2005065654 - PREPARATIONS DE ROSIGLITAZONE

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

What is claimed is:
1. A dosage formulation, comprising:

an active agent, wherein the active agent is amorphous rosiglitazone or an amorphous pharmaceutically acceptable salt thereof; and

a pharmaceutically acceptable polymeric carrier, wherein the polymeric carrier maintains the active agent in substantially amorphous form.

2. The dosage formulation of Claim 1, wherein the polymeric carrier is an ion-exchange resin, a reducing solvent, a hydroxypropyl cellulose, a methyl cellulose, a carboxymethyl cellulose, a sodium carboxymethyl cellulose, a cellulose acetate phthalate, a cellulose acetate butyrate, a hydroxyethyl cellulose, a ethyl cellulose, a polyvinyl alcohol, a polypropylene, a dextran, a dextrin, a hydroxypropyl-beta-cyclodextrin, chitosan, a co(lactic/glycolid) copolymer, a poly(orthoester), a poly(anhydrate), a polyvinyl chloride, a polyvinyl acetate, an ethylene vinyl acetate, a lectin, a carbopol, a silicon elastomer, a polyacrylic polymer, a maltodextrin, polyvinylpynolidone, crosslinked polyvinylpyπolidone, a polyethylene glycol, an alpha-cyclodextrins, a beta-cyclodextrin, a gamma-cyclodextrin, or a combination comprising one or more of the foregoing polymeric carriers.

3. The dosage formulation of Claim 1, wherein the polymeric carrier comprises crosslinked polyvinylpynolidone.

4. The dosage fonnulation of Claim 1, wherein the active agent is rosiglitazone maleate.

5. The dosage formulation of Claim 1, wherein the weight ratio of polymeric carrier to active agent is about 20:1 to about 0.5:1.

6. The dosage formulation of Claim 1, further comprising an excipient, wherein the excipient is a diluent, a binder, a disintegrant, a coloring agent, a flavoring agent, a lubricant, a preservative, or a combination comprising one or more of the foregoing excipients.

7. The dosage formulation of Claim 1, wherein the formulation is in the form of a tablet, a capsule, a soft-gel, or a powder.

8. The dosage formulation of Claim 1, wherein the formulation provides an AUC between 0 and 24 hours after administration that is more than 80 percent and less than 120 percent of the AUC provided by an equivalent weight of AVANDIA® between 0 and 24 hours after administration.

9. A process for preparing an amorphous active agent comprising amorphous rosiglitazone or an amorphous pharmaceutically acceptable salt thereof, comprising:

mixing rosiglitazone or pharmaceutically acceptable salt thereof with a solvent and a pharmaceutically acceptable polymeric carrier; and

drying to form a composition comprising the amorphous rosiglitazone or the pharmaceutically acceptable salt thereof and the polymeric carrier.

10. The process of Claim 9, wherein the solvent comprises water.

11. The process of Claim 9, wherein the composition is an immediate-release formulation, a sustained-release formulation, or a combination comprising one or more of the foregoing foπnulations.

12. The process of Claim 9, wherein the pharmaceutically acceptable salt of rosiglitazone is rosiglitazone maleate.

13. The process of Claim 9, wherein the rosiglitazone is mixed as a free base form, and wherein the process further comprises adding an acid conesponding to the pharmaceutically acceptable salt of the rosiglitazone.

14. The process of Claim 13, wherein the molar ratio of the rosiglitazone or pharmaceutically acceptable salt thereof to acid is about 1:1 to about 1:1.8.

15. The process of Claim 9, wherein the polymeric carrier is an ion-exchange resin, a reducing solvent, a hydroxypropyl cellulose, a methyl cellulose, a carboxymethyl cellulose, a sodium carboxymethyl cellulose, a cellulose acetate phthalate, a cellulose acetate butyrate, a hydroxyethyl cellulose, a ethyl cellulose, a polyvinyl alcohol, a polypropylene, a dextran, a dextrin, a hydroxypropyl-beta-cyclodextrin, chitosan, a co(lactic/glycolid) copolymer, a poly(orthoester), a poly(anhydrate), a polyvinyl chloride, a polyvinyl acetate, an ethylene vinyl acetate, a lectin, a carbopol, a silicon elastomer, a polyacrylic polymer, a maltodextrin, polyvinylpynolidone, crosslinked polyvinylpynolidone, a polyethylene glycol, an alpha-cyclodextrins, a beta-cyclodextrin, a gamma-cyclodextrin, or a combination comprising one or more of the foregoing polymeric carriers.

16. The process of Claim 15, wherein the weight ratio of the polymeric carrier to the rosiglitazone or pharmaceutically acceptable salt thereof is about 20:1 to about 0.5:1.

17. The process of Claim 9, wherein the drying comprises spray drying.

18. A pharmaceutical composition, comprising:

amorphous rosiglitazone maleate and a polymeric carrier as prepared by the process of Claim 9.

19. The pharmaceutical composition of claim 18, wherein the composition provides an AUC between 0 and 24 hours after administration that is more than 80 percent and less than 120 percent of the AUC provided by an equivalent weight of AVANDIA® between 0 and 24 hours after administration.

20. A controlled-release oral dosage form comprising rosiglitazone or a pharmaceutically acceptable salt thereof dispersed in a solid polymeric matrix, wherein the solid polymeric matrix swells upon imbition of water, wherein the solid polymeric matrix retains greater than or equal to about 40 weight percent of the rosiglitazone one hour after immersion in simulated gastric fluid, and wherein the solid polymeric matrix remains substantially intact until substantially all of the rosiglitazone or pharmaceutically acceptable salt thereof is released.

21. The dosage form of Claim 20, wherein the solid polymeric matrix releases substantially all of the rosiglitazone or pharmaceutically acceptable salt thereof within eight hours of immersion in simulated gastric fluid.

22. The dosage form of Claim 20, wherein the rosiglitazone or pharmaceutically acceptable salt thereof is in amorphous form.

23. The dosage form of Claim 20, wherein the pharmaceutically acceptable salt of rosiglitazone is rosiglitazone maleate.

24. The dosage form of Claim 20, wherein the ratio of the rosiglitazone or pharmaceutically acceptable salt thereof to the polymeric matrix is about 15:85 to about 80:20.

25. The dosage form of Claim 20, wherein the polymeric matrix is a cellulose, an alkyl-substituted cellulose, a poly(alkylene oxide), a polysaccharide gum, a polyacrylic acid, or a combination comprising one or more of the foregoing matrices.

26. The dosage form of Claim 25, wherein the alkyl cellulose is a hydroxymethyl cellulose, a hydroxyethyl cellulose, a hydroxypropyl cellulose, a hydroxypropyl methylcellulose, a carboxymethyl cellulose, or a combination comprising one or more of the foregoing alkyl celluloses.

27. The dosage form of Claim 25, wherein the poly(alkylene oxide) is poly(ethylene oxide).

28. The dosage form of Claim 27, wherein the poly(ethylene oxide) has a molecular weight of greater than or equal to about 4,000,000.

29. The dosage form of Claim 25, wherein the polyacrylic acid is a crosslinked polyacrylic acid.

30. The dosage form of Claim 25, wherein the polysaccharide gum is xantham gum.

31. The dosage form of Claim 20, wherein the solid polymeric matrix retains greater than or equal to about 60 weight percent of the rosiglitazone or pharmaceutically acceptable salt thereof after one hour of immersion in simulated gastric fluid.

32. The dosage form of Claim 20, wherem the solid polymeric matrix retains greater than or equal to about 80 weight percent of the rosiglitazone or pharmaceutically acceptable salt thereof after one hour of immersion in simulated gastric fluid.

33. The dosage form of Claim 20, further comprising a hydrophobic additive to further retard the release of the rosiglitazone or pharmaceutically acceptable salt thereof.

34. The dosage form of Claim 33, wherein the hydrophobic additive is glyceryl monostearate, sodium myristate, or a combination comprising one or more of the foregoing additives.

35. A pulsed-release dosage form comprising:

an immediate-release dosage form comprising rosiglitazone or a pharmaceutically acceptable salt thereof; and

a delayed-release dosage form comprising rosiglitazone or a pharmaceutically acceptable salt thereof.

36. The pulsed-release dosage fonn of Claim 35, wherein the delayed-release dosage form comprises a higher concentration of the rosiglitazone or pharmaceutically acceptable salt thereof than the immediate-release dosage form.

37. The pulsed-release dosage form of Claim 35, wherein the delayed-release dosage form is in the form of a core and the immediate-release dosage form is in the form of a coating sunounding the core.

38. The pulsed-release dosage form of Claim 37, wherein the core comprises an absorption enhancer.

39. The pulsed-release dosage form of Claim 38, wherein the absorption enhancer is capric acid, oleic acid, sodium lauryl sulfate, sodium taurocholate and polysorbate 80, citric acid, phytic acid, ethylenediamine tetraacetic acid, ethylene glycol-bis((S-aminoethyl ether)-N,N,N,N-tetraacetic acid, or a combination comprising one or more of the foregoing absorption enhancers.

40. The pulsed-release dosage form of Claim 37, wherein the core comprises a water swellable substance.

41. The pulsed-release dosage form of Claim 40, wherein the water swellable substance is a hydroxypropyl cellulose, a cross-linked polyvinyl pynolidone, a cross-linked sodium carboxymethylcellulose, a sodium starch glycollate, a sodium carboxymethyl starch, an ion exchange resin, a starch, a preglatinized starch, a formalin-casein, or a combination comprising one or more of the foregoing water-swellable substances.

42. The pulsed-release dosage form of Claim 37, wherein the core further comprises an osmotic agent.

43. The pulsed-release dosage form of Claim 42, wherein the osmotic agent is magnesium sulfate, sodium chloride, lithium chloride, potassium chloride, potassium sulfate, sodium carbonate, lithium sulfate, calcium bicarbonate, sodium sulfate, calcium lactate, urea, magnesium succinate, sucrose, or a combination comprising one or more of the foregoing osmotic agents.

44. The pulsed-release dosage form of Claim 37, wherein the dosage form further comprises a lag time controlling layer disposed on the core.

45. The pulsed-release dosage form of Claim 44, wherein the lag time controlling layer is a cellulose acetate, an ethylcellulose, a polyvinyl acetate, a cellulose acetate butyrate, a cellulose acetate propionate, an acrylic acid copolymer, or a combination comprising one or more of the foregoing polymers.

46. The pulsed-release dosage form of Claim 35, wherein the delayed-release dosage form is in the form of pellets.

47. The pulsed-release dosage form of Claim 46, wherein the pellets comprise an absorption enhancer.

48. The pulsed-release dosage form of Claim 47, wherein the absorption enhancer is capric acid, oleic acid, sodium lauryl sulfate, sodium taurocholate and polysorbate 80, citric acid, phytic acid, ethylenediamine tetraacetic acid, ethylene glycol-bis(j3-aminoethyl ether)-N,N,N,N-tetraacetic acid, or a combination comprising one or more of the foregoing absorption enhancers.

49. The pulsed-release dosage form of Claim 35, wherein the Cmax of the delayed-release dosage form occurs between 1 to about 12 hours after administration to a human in the absence of food.

50. A controlled-release dosage form comprising rosiglitazone or a
pharmaceutically acceptable salt thereof, wherein a peak plasma concentration occurs greater than 1 hour after administration to a human in the absence of food.

51. The controlled-release dosage form of Claim 50, wherein the peak plasma concentration occurs greater than 2 hours after administration to a human in the absence of food.

52. The controlled-release dosage form of Claim 50, wherein the peak plasma concentration occurs greater than 4 hours after administration to a human in the absence of food.

53. The controlled-release dosage form of Claim 50, wherein the pharmaceutically acceptable salt of rosiglitazone is rosiglitazone maleate.

54. The controlled-release dosage form of Claim 50, wherein the rosiglitazone or pharmaceutically acceptable salt thereof is in amorphous form.

55. A controlled-release dosage form comprising rosiglitazone or a
pharmaceutically acceptable salt thereof and an excipient, wherein less than 75 wt%> of the rosiglitazone or pharmaceutically acceptable salt thereof is released at 1 hour after immersion in simulated gastric fluid.

56. The controlled-release dosage fonn of Claim 55, wherein less than 60 wt% of the rosiglitazone or pharmaceutically acceptable salt thereof is released at 1 hour after immersion in simulated gastric fluid.

57. The controlled-release dosage form of Claim 55, wherein less than 50 wt% of the rosiglitazone or pharmaceutically acceptable salt thereof is released at 1 hour after immersion in simulated gastric fluid.

58. The controlled-release dosage fonn of Claim 55, wherein less than 40 wt% of the rosiglitazone or pharmaceutically acceptable salt thereof is released at 1 hour after immersion in simulated gastric fluid.

59. The controlled-release dosage form of Claim 55, wherein the pharmaceutically acceptable salt of rosiglitazone is rosiglitazone maleate.

60. The controlled-release dosage form of Claim 55, wherein the rosiglitazone of phannaceutically acceptable salt thereof is in amorphous form.

61. A dosage foπn comprising rosiglitazone or a pharmaceutically acceptable salt thereof, and nateglinide or a pharmaceutically acceptable salt thereof.