Pharmaceutical compositions

1. A method of treating IgA nephropathy in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising one or more cores comprising budesonide;

wherein the one or more cores are coated with an extended release pharmaceutically-acceptable polymeric blend comprising a water-insoluble polymer having a solubility in water (at 25° C.) of less than about 0.1 mg/mL and a pore-forming polymer having a solubility in water (at 25° C.) of at least about 10 mg/mL;

wherein the water-insoluble polymer is present in an amount of from about 47 wt. % to about 56 wt. % of the extended release pharmaceutically-acceptable polymeric blend and the pore-forming polymer is present in an amount of from about 32 wt. % to about 22 wt. % of the extended release pharmaceutically-acceptable polymeric blend;

wherein the extended release pharmaceutically-acceptable polymeric blend is present in an amount of from 5 wt. % to about 18 wt. % of the total coated core weight;

wherein the pharmaceutical composition is orally administered as a capsule that comprises an enteric coating in an amount of from about 34 mg to about 46 mg per capsule;

wherein the pharmaceutical composition meets the following release profile in a standard in vitro USP<711>dissolution test using a dissolution apparatus according to Apparatus 2 (Paddle Apparatus) at a paddle rotation speed of 100 rpm:

a) no more than about 10% of the budesonide is released into an aqueous dissolution medium with a pH of about 1.2 within about 120 minutes;

b) no more than about 10% of the budesonide is released into a pharmaceutically-relevant dissolution medium within about 30 minutes, wherein the pharmaceutically-relevant dissolution medium is a Level 1 Fasted State Simulated Intestinal Fluid at a pH of about 6.5, or a phosphate buffer medium at a pH of about 6.8; and

c) at least about 70% of the budesonide is released into the pharmaceutically-relevant dissolution medium within about 120 minutes; and

wherein the subject is administered a daily dose of about 16 mg of budesonide.

2. The method according to claim 1 , wherein the water-insoluble polymer is an alkyl cellulose.

3. The method according to claim 2 , wherein the alkyl cellulose is an ethyl cellulose.

4. The method according to claim 1 , wherein the pore-forming polymer is selected from polyethylene glycol (PEG), hydroxypropylmethyl cellulose (HPMC), and hydroxypropyl cellulose (HPC).

5. The method according to claim 1 , wherein the water-insoluble polymer is an alkyl cellulose and the pore-forming polymer is selected from polyethylene glycol (PEG), hydroxypropylmethyl cellulose (HPMC), and hydroxypropyl cellulose (HPC).

6. The method according to claim 1 , wherein the extended release pharmaceutically-acceptable polymeric blend is present in an amount of from about 6 wt. % to about 13 wt. % of the total coated core weight.

7. The method according to claim 1 , wherein the water-insoluble polymer and the pore-forming polymer are coalesced to form the extended release pharmaceutically-acceptable polymeric blend by curing the coated cores at a temperature of from about 55° C. to about 75° C. for about 1 hour to about 10 hours.

8. The method according to claim 1 , wherein the budesonide is substantially released to the ileum region of the small intestine in the subject.

9. The method according to claim 1 , wherein the pharmaceutically-relevant dissolution medium is a Level 1 Fasted State Simulated Intestinal Fluid at a pH of about 6.5.

10. The method according to claim 9 , wherein the Level 1 Fasted State Simulated Intestinal Fluid comprises an added surfactant.

11. The method according to claim 10 , wherein the added surfactant is present in an amount of about 0.5 mg/mL.

12. The method according to claim 1 , wherein the pharmaceutically-relevant dissolution medium is a phosphate buffer medium at a pH of about 6.8.

13. The method according to claim 12 , wherein the phosphate buffer medium comprises an added surfactant.

14. The method according to claim 13 , wherein the surfactant is present in an amount of about 0.5 mg/mL.

15. The method according to claim 1 , wherein the capsule is a size 1 capsule.

16. A method of treating IgA nephropathy in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising one or more cores comprising budesonide;

wherein the one or more cores are coated with an extended release pharmaceutically-acceptable polymeric blend comprising an alkyl cellulose and a pore-forming polymer selected from polyethylene glycol (PEG), hydroxypropylmethyl cellulose (HPMC), and hydroxypropyl cellulose (HPC);

wherein the alkyl cellulose is present in an amount of from about 47 wt. % to about 56 wt. % of the extended release pharmaceutically-acceptable polymeric blend and the pore-forming polymer is present in an amount of from about 32 wt. % to about 22 wt. % of the extended release pharmaceutically-acceptable polymeric blend;

wherein the extended release pharmaceutically-acceptable polymeric blend is present in an amount of from 5 wt. % to about 18 wt. % of the total coated core weight;

wherein the pharmaceutical composition is orally administered as a capsule that comprises an enteric coating in an amount of from about 34 mg to about 46 mg per capsule;

wherein the pharmaceutical composition meets the following release profile in a standard in vitro USP<711>dissolution test using a dissolution apparatus according to Apparatus 2 (Paddle Apparatus) at a paddle rotation speed of 100 rpm:

a) no more than about 10% of the budesonide is released into an aqueous dissolution medium with a pH of about 1.2 within about 120 minutes;

b) no more than about 10% of the budesonide is released into a pharmaceutically-relevant dissolution medium within about 30 minutes, wherein the pharmaceutically-relevant dissolution medium is a Level 1 Fasted State Simulated Intestinal Fluid at a pH of about 6.5, or a phosphate buffer medium at a pH of about 6.8; and

c) at least about 70% of the budesonide is released into the pharmaceutically-relevant dissolution medium within about 120 minutes; and

wherein the subject is administered a daily dose of about 16 mg of budesonide.

17. The method according to claim 16 , wherein the alkyl cellulose is an ethyl cellulose.

18. The method according to claim 16 , wherein the pore-forming polymer is PEG.

19. The method according to claim 16 , wherein the pore-forming polymer is HPMC.

20. The method according to claim 16 , wherein the pore-forming polymer is HPC.

21. The method according to claim 16 , wherein the extended release pharmaceutically-acceptable polymeric blend is present in an amount of from about 6 wt. % to about 13 wt. % of the total coated core weight.

22. The method according to claim 16 , wherein the budesonide is substantially released to the ileum region of the small intestine in the subject.

23. The method according to claim 16 , wherein the pharmaceutically-relevant dissolution medium is a Level 1 Fasted State Simulated Intestinal Fluid at a pH of about 6.5.

24. The method according to claim 23 , wherein the Level 1 Fasted State Simulated Intestinal Fluid comprises an added surfactant.

25. The method according to claim 24 , wherein the added surfactant is present in an amount of about 0.5 mg/mL.

26. The method according to claim 16 , wherein the pharmaceutically-relevant dissolution medium is a phosphate buffer medium at a pH of about 6.8.

27. The method according to claim 26 , wherein the phosphate buffer medium comprises an added surfactant.

28. The method according to claim 27 , wherein the surfactant is present in an amount of about 0.5 mg/mL.

29. The method according to claim 16 , wherein the capsule is a size 1 capsule.

30. The method according to claim 16 , wherein the water-insoluble polymer and the pore-forming polymer are coalesced to form the extended release pharmaceutically-acceptable polymeric blend by curing the coated cores at a temperature of from about 55° C. to about 75° C. for about 1 hour to about 10 hours.