Recherche dans les collections de brevets nationales et internationales
Certains contenus de cette application ne sont pas disponibles pour le moment.
Si cette situation persiste, veuillez nous contacter àObservations et contact
1. (WO2005065663) PREPARATIONS DE ROSIGLITAZONE ET DE METFORMINE
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 controlled-release oral dosage form comprising rosiglitazone or a pharmaceutically acceptable salt thereof, and metformin 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 or phannaceutically acceptable salt thereof 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.

2. The dosage form of Claim 1, 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.

3. The dosage form of Claim 1 , wherein the rosiglitazone or phannaceutically acceptable salt thereof is in amoφhous form.

4. The dosage form of Claim 1, wherein the rosiglitazone or pharmaceutically acceptable salt thereof is rosiglitazone maleate.

5. The dosage form of Claim 1, wherein the metformin or phannaceutically acceptable salt thereof is metformin hydrochloride.

6. The dosage form of Claim 1, wherein the ratio of the rosiglitazone or pharmaceutically acceptable salt thereof and the metformin or pharmaceutically acceptable salt thereof to the solidpolymeric matrix is about 15:85 to about 80:20.

7. The dosage form of Claim 1, wherein the solid 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.

8. The dosage form of Claim 7, 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.

9. The dosage form of Claim 8, wherein the poly(alkylene oxide) is poly(ethylene oxide).

10. The dosage form of Claim 9, wherein the poly(ethylene oxide) has a molecular weight of greater than or equal to about 4,000,000.

11. The dosage form of Claim 7, wherein the polyacrylic acid is a crosslinked polyacrylic acid.

12. The dosage form of Claim 7, wherein the polysaccharide gum is xantham gum.

13. The dosage form of Claim 1, 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.

14. The dosage form of Claim 1, wherein the solid polymeric matrix retains greater than or equal to about 80 weight percent of the rosiglitazone or phannaceutically acceptable salt thereof, after one hour of immersion in simulated gastric fluid.

15. The dosage form of Claim 1, further comprising a hydrophobic additive to further retard the release of the rosiglitazone or pharmaceutically acceptable salt thereof.

16. The dosage form of Claim 15 wherein the hydrophobic additive is glyceryl monostearate, sodium myristate, or a combination comprising one or more of the foregoing additives.

17. A dosage formulation, comprising:

amoφhous rosiglitazone or an amoφhous pharmaceutically acceptable salt thereof;

metformin or a pharmaceutically acceptable salt thereof; and

a phannaceutically acceptable polymeric carrier, wherein the polymeric carrier maintains the rosiglitazone or pharmaceutically acceptable salt thereof in substantially amoφhous form.

18. The dosage formulation of Claim 17, 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, polyvinylpyrrohdone, crosslinked polyvmylpynolidone, a polyethylene glycol, an alpha-cyclodextrins, a beta-cyclodextrin, a gamma-cyclodextrin, or a combination comprising one or more of the foregoing polymeric carriers.

19. The dosage formulation of Claim 17, wherein the polymeric carrier comprises crosslinked polyvinylpyrrohdone.

20. The dosage formulation of Claim 17, wherein the pharmaceutically acceptable salt of rosiglitazone is rosiglitazone maleate.

21. The dosage formulation of Claim 17, wherein the weight ratio of the polymeric carrier to the rosiglitazone or pharmaceutically acceptable salt thereof is about 0.4:1 to 20:1.

22. The dosage formulation of Claim 17, 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.

23. The dosage formulation of Claim 17, wherein the formulation is in the form of a tablet, a capsule, a soft-gel, or a powder.

24. The dosage formulation of Claim 17, wherein the fonnulation 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 the marketed formulation of rosiglitazone and metformin between 0 and 24 hours after administration.

25. A controlled-release dosage form comprising a pharmaceutically effective amount of rosiglitazone or a pharmaceutically acceptable salt thereof, and a pharmaceutically effective amount of metformin or a pharmaceutically acceptable salt thereof, exhibiting a dissolution profile such that

at 1 hour after immersion in simulated gastric fluid, 40 wt% to 80 wt%> of the metformin or pharmaceutically acceptable salt thereof is released;

at 2 hours after immersion in simulated gastric fluid, 60 wt% to 85 wt% of the metformin or pharmaceutically acceptable salt thereof, is released; and

at 5 hours after immersion in simulated gastric fluid, 90 wt%> to 100 wt% of the metformin or pharmaceutically acceptable salt thereof, is released.

26. A controlled-release dosage form comprising a pharmaceutically effective amount of rosiglitazone or pharmaceutically acceptable salt thereof, and a pharmaceutically effective amount of metfonnin or pharmaceutically acceptable salt thereof,

exhibiting a dissolution profile such that at 7 hours after immersion in simulated gastric fluid, less than 80 wt% of the metformin or pharmaceutically acceptable salt thereof, is released.

27. A controlled-release dosage form comprising a pharmaceutically effective amount of rosiglitazone or pharmaceutically acceptable salt thereof, and a pharmaceutically effective amount of metformin or pharmaceutically acceptable salt thereof,

exhibiting a dissolution profile such that

at 1 hour after immersion in simulated gastric fluid, less than or equal to 25 wt% of the metfonnin or phannaceutically acceptable salt thereof is released;

at 2 hours after immersion in simulated gastric fluid, 15 wt% to 40 wt% of the metformin or pharmaceutically acceptable salt thereof is released;

at 3 hours after immersion in simulated gastric fluid, 25 wt% to 50 wt%> of the metfonnin or pharmaceutically acceptable salt thereof, is released; and

at 5 hours after immersion in simulated gastric fluid, 40 wt% to 70 wt% of the rosiglitazone or pharmaceutically acceptable salt thereof, and metformin or pharmaceutically acceptable salt thereof, is released.

28. A controlled-release dosage form comprising a pharmaceutically effective amount of rosiglitazone or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable amount of metformin 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.

29. The controlled-release dosage form of Claim 28, wherein the peak plasma concentration occurs greater than 2 hours after administration to a human in the absence of food.

30. The controlled-release dosage form of Claim 28, wherein the peak plasma concentration occurs greater than 4 hours after administration to a human in the absence of food.

31. The controlled-release dosage form of Claim 28, wherein the pharmaceutically acceptable salt of rosiglitazone is rosiglitazone maleate

32. The controlled-release dosage form of Claim 28, wherein the rosiglitazone or pharmaceutically acceptable salt thereof is in amoφhous form.

33. A controlled-release dosage form comprising a pharmaceutically effective amount of rosiglitazone or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable amount of metfonnin or a phannaceutically acceptable sale 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.

34. The controlled-release dosage form of Claim 33, wherein less than 60 wt% of the rosiglitazone or pharmaceutically acceptable salt thereof is released at 1 hour after immersion in simulated gastric fluid.

35. The controlled-release dosage form of Claim 33, wherein less than 50 wt% of the rosiglitazone or phannaceutically acceptable salt thereof is released at 1 hour after immersion in simulated gastric fluid.

36. The controlled-release dosage form of Claim 33, wherein less than 40 wt% of the rosiglitazone or pharmaceutically acceptable salt thereof is released at 1 hour after immersion in simulated gastric fluid.