Pharmaceutical compositions
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.
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 ethylcellulose in an amount of about 51.8 wt. % of the extended release pharmaceutically-acceptable polymeric blend and hydroxypropylmethyl cellulose in an amount of about 27.3 wt. % of the extended release pharmaceutically-acceptable polymeric blend;
wherein the extended release pharmaceutically-acceptable polymeric blend is present in an amount of from about 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 of claim 1 , wherein the budesonide is substantially released to the ileum region of the small intestine in the subject.
3. The method of claim 2 , wherein at least about 60% of the initial content of budesonide is released to the ileum region of the small intestine in the subject.
4. The method of claim 2 , wherein at least about 90% of the initial content of budesonide is released to the ileum region of the small intestine in the subject.
5. The method of claim 1 , wherein the pharmaceutically-relevant dissolution medium is a Level 1 Fasted State Simulated Intestinal Fluid at a pH of about 6.5.
6. The method of claim 1 , wherein the pharmaceutically-relevant dissolution medium is a phosphate buffer medium at a pH of about 6.8.
7. 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 ethylcellulose in an amount of from about 47 wt. % to about 56 wt. % of the extended release pharmaceutically-acceptable polymeric blend and hydroxypropylmethyl cellulose 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 about 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.
8. The method of claim 7 , 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.
9. The method of claim 7 , wherein the extended release pharmaceutically-acceptable polymeric blend is present in an amount of 9.1 wt. % (±2%) of the total coated core weight.
10. The method of claim 9 , wherein the budesonide is substantially released to the ileum region of the small intestine in the subject.
11. The method of claim 10 , wherein at least about 60% of the initial content of budesonide is released to the ileum region of the small intestine in the subject.
12. The method of claim 10 , wherein at least about 90% of the initial content of budesonide is released to the ileum region of the small intestine in the subject.
13. The method of claim 7 , wherein the pharmaceutically-relevant dissolution medium is a Level 1 Fasted State Simulated Intestinal Fluid at a pH of about 6.5.
14. The method of claim 7 , wherein the pharmaceutically-relevant dissolution medium is a phosphate buffer medium at a pH of about 6.8.
15. The method of claim 5 , wherein the Level 1 Fasted State Simulated Intestinal Fluid comprises an added surfactant.
16. The method of claim 15 , wherein the added surfactant is present in an amount of about 0.5 mg/mL.
17. The method of claim 6 , wherein the phosphate buffer medium comprises an added surfactant.
18. The method of claim 17 , wherein the surfactant is present in an amount of about 0.5 mg/mL.
19. The method of claim 13 , wherein the Level 1 Fasted State Simulated Intestinal Fluid comprises an added surfactant.
20. The method of claim 19 , wherein the added surfactant is present in an amount of about 0.5 mg/mL.
21. The method of claim 14 , wherein the phosphate buffer medium comprises an added surfactant.
22. The method of claim 21 , wherein the surfactant is present in an amount of about 0.5 mg/mL.
23. The method of claim 1 , wherein the capsule is a size 1 capsule.
24. The method of claim 7 , wherein the capsule is a size 1 capsule.
25. The method of 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.
26. The method of claim 1 , wherein the ethylcellulose is present in an amount of 51.8 wt. % (±2%) of the extended release pharmaceutically-acceptable polymeric blend, the hydroxypropylmethyl cellulose is present in an amount of 27.3 wt. % (±2%) of the extended release pharmaceutically-acceptable polymeric blend, the extended release pharmaceutically-acceptable polymeric blend is present in an amount of 9.1 wt. % (±2%) of the total coated core weight, and the capsule is a size 1 capsule.