Claims for Patent: 12,171,882

Summary for Patent: 12,171,882

Title:	Pharmaceutical compositions
Abstract:	The present invention provides for a method of treatment of IgA nephropathy, which method comprises: (i) identifying a pharmaceutically acceptable composition intended to treat IgA nephropathy comprising budesonide and one or more pharmaceutically-acceptable excipients that provide for a modified release of said budesonide after administration to the gastrointestinal tract, which composition fulfils the following requirements in a standard in vitro USP<711>/Ph.Eur. 2.9.3 dissolution test using a dissolution apparatus according to Apparatus 2 (Paddle Apparatus) of said test; (a) the composition fulfils the requirement that no more than about 10% of the budesonide is released into the dissolution medium within about 120 minutes, when the dissolution medium is aqueous and has a pH of about 1.2; (b) the composition fulfils the requirement that no more than about 10% of the budesonide is released into a pharmaceutically-relevant dissolution medium within about 30 minutes; and (c) the composition fulfils the requirement that at least about 70% of the budesonide is released into the pharmaceutically-relevant dissolution medium within about 120 minutes; (ii) wherein the method comprises the step of administering said composition to a patient with IgA nephropathy in need of said treatment.
Inventor(s):	Eva Kristina RIESEL, Lena Margareta PERESWETOFF-MORATH, Kari SANDVOLD, Christian Olle Andreas PEDERSEN
Assignee:	Calliditas Therapeutics AB
Application Number:	US18/392,602
Patent Claims:	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.