IP Library Granted Patent US 12,311,057
Granted Patent B2
US 12,311,057 · App. 18/934,978 · Granted May 27, 2025

Pharmaceutical compositions

Inventors: Eva Kristina Riesel (Mölndal, SE); Lena Margareta Pereswetoff-Morath (Spånga, SE); Kari Sandvold (Uppsala, SE); Christian Olle Andreas Pedersen (Uppsala, SE)
Assignee: CALLIDITAS THERAPEUTICS AB
A61K9/4891A61K9/2846A61K9/5047A61K31/58A61P13/12
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Quick Facts
Patent No.
US 12,311,057
App. No.
18/934,978
Granted
May 27, 2025
Kind
B2
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.

Claims (37)

1. A pharmaceutical composition comprising:

a plurality of cores comprising budesonide encapsulated within a capsule comprising an enteric coating, wherein the plurality of cores are each 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 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.

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

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

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

5. The pharmaceutical composition 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 pharmaceutical composition 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 pharmaceutical composition 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 pharmaceutical composition 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.

9. The pharmaceutical composition according to claim 8 , wherein the Level 1 Fasted State Simulated Intestinal Fluid comprises an added surfactant.

10. The pharmaceutical composition according to claim 9 , wherein the added surfactant is present in an amount of about 0.5 mg/mL.

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

12. The pharmaceutical composition according to claim 11 , wherein the phosphate buffer medium comprises an added surfactant.

13. The pharmaceutical composition according to claim 12 , wherein the surfactant is present in an amount of about 0.5 mg/mL.

14. The pharmaceutical composition according to claim 1 , where the enteric coating is present in an amount of from about 34 mg to about 46 mg per capsule.

15. The pharmaceutical composition according to claim 1 , where the enteric coating is present in an amount of from about 36 mg to about 40 mg per capsule.

16. The pharmaceutical composition according to claim 1 , wherein the capsule is a size 1 capsule.

17. The pharmaceutical composition according to claim 1 , wherein the capsule comprises about 4 mg of budesonide.

18. A method of treating IgA nephropathy in a subject in need thereof, comprising:

orally administering to the subject the pharmaceutical composition of claim 1 at a daily dose of about 16 mg of budesonide.

19. The method according to claim 18 , wherein the water-insoluble polymer is an alkyl cellulose.

20. The method according to claim 19 , wherein the alkyl cellulose is an ethyl cellulose.

21. The method according to claim 18 , wherein the pore-forming polymer is selected from polyethylene glycol (PEG), hydroxypropylmethyl cellulose (HPMC), and hydroxypropyl cellulose (HPC).

22. The method according to claim 18 , 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).

23. The method according to claim 18 , 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.

24. The method according to claim 18 , 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.

25. The method according to claim 18 , wherein the pharmaceutical composition is orally administered to the subject at least one hour before a meal.

26. The method according to claim 18 , wherein the pharmaceutical composition is orally administered once daily.

27. The method according to claim 18 , wherein the pharmaceutical composition is orally administered in the morning at least one hour before the first meal of the day.

28. The method according to claim 18 , where the enteric coating is present in an amount of from about 34 mg to about 46 mg per capsule.

29. The method according to claim 18 , where the enteric coating is present in an amount of from about 36 mg to about 40 mg per capsule.

30. The method according to claim 18 , wherein the capsule is a size 1 capsule.

Priority Claims (2)
GB 2217146 · Nov 16, 2022 · national
GB 2217150 · Nov 16, 2022 · national
Continuity (5)
Continuation 18392602 · Dec 21, 2023
Continuation 18100396 · Jan 23, 2023
Provisional Application 63302216 · Jan 24, 2022
Provisional Application 63302226 · Jan 24, 2022
Related Publication 20250057775A1 · Feb 20, 2025
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