Compositions of obeticholic acid and methods of use
The disclosure relates to obeticholic acid formulations with improved stability, dissolution, and/or solubility, methods of preparing the same for use and methods of treating various diseases and conditions.
1. A method of treating primary biliary cholangitis (PBC) in a subject in need thereof, said method comprising administering to the subject a tablet comprising an intra-granular portion and an extra-granular portion, the intra-granular portion comprising obeticholic acid or a pharmaceutically acceptable salt or amino acid conjugate thereof in an amount of about 1 mg to about 50 mg, and one or more pharmaceutically acceptable excipients, and the extra-granular portion comprising one or more pharmaceutically acceptable excipients,
wherein at least one pharmaceutically acceptable excipient in the tablet has an alcohol content of less than about 6% (w/w);
wherein the amount is a starting dose, an adjusted dose or a re-adjusted dose; and
wherein the tablet is administered daily (QD), every other day (Q2D), once a week (QW), twice a week (BID), three times a week (TIW), once a month (QM), or twice a month (Q2M).
2. The method of claim 1 , wherein the amount is about 1 mg to about 10 mg.
3. The method of claim 1 , wherein the intra-granular portion comprises obeticholic acid.
4. The method of claim 1 , wherein the amount is a starting dose and the tablet is administered in a titration period.
5. The method of claim 4 , wherein the titration period is from 1 month to 6 months.
6. The method of claim 5 , wherein the titration period is 3 months or 6 months.
7. The method of claim 1 , wherein the amount is 10 mg, and the tablet is administered daily.
8. The method of claim 1 , wherein the amount is 5 mg, and the tablet is administered daily.
9. The method of claim 1 , wherein the amount is about 1 mg to about 5 mg, and the tablet is administered daily.
10. The method of claim 1 , wherein the method further comprises administering to the subject a bile acid binding resin at least 4 hours before the tablet is administered.
11. The method of claim 1 , wherein the method further comprises administering to the subject a bile acid binding resin at least 4 hours after the tablet is administered.
12. A method of treating primary biliary cholangitis (PBC) in a subject in need thereof, said method comprising administering to the subject a tablet comprising obeticholic acid or a pharmaceutically acceptable salt or amino acid conjugate thereof in an amount of about 1 mg to about 50 mg, and one or more pharmaceutically acceptable excipients,
wherein the obeticholic acid or the pharmaceutically acceptable salt or amino acid conjugate thereof is in the form of jet-milled particles, and wherein at least 50% of the particles have a diameter of 200 μm or less;
wherein at least one pharmaceutically acceptable excipient in the tablet has an alcohol content of less than about 6% (w/w);
wherein the amount is a starting dose, an adjusted dose or a re-adjusted dose; and
wherein the tablet is administered daily (QD), every other day (Q2D), once a week (QW), twice a week (BID), three times a week (TIW), once a month (QM), or twice a month (Q2M).
13. The method of claim 12 , wherein the amount is about 1 mg to about 10 mg.
14. The method of claim 12 , wherein the tablet comprises obeticholic acid.
15. The method of claim 12 , wherein the amount is a starting dose and the tablet is administered in a titration period.
16. The method of claim 15 , wherein the titration period is from 1 month to 6 months.
17. The method of claim 16 , wherein the titration period is 3 months or 6 months.
18. The method of claim 12 , wherein the amount is 10 mg, and the tablet is administered daily.
19. The method of claim 12 , wherein the amount is 5 mg, and the tablet is administered daily.
20. The method of claim 12 , wherein the amount is about 1 mg to about 5 mg, and the tablet is administered daily.
21. The method of claim 12 , wherein the method further comprises administering to the subject a bile acid binding resin at least 4 hours before the tablet is administered.
22. The method of claim 12 , wherein the method further comprises administering to the subject a bile acid binding resin at least 4 hours after the tablet is administered.
23. A method of treating primary biliary cholangitis (PBC) in a subject in need thereof, said method comprising administering to the subject a tablet comprising an intra-granular portion and an extra-granular portion, the intra-granular portion comprising obeticholic acid or a pharmaceutically acceptable salt or amino acid conjugate thereof in an amount of about 1 mg to about 50 mg, and one or more pharmaceutically acceptable excipients, and the extra-granular portion comprising one or more pharmaceutically acceptable excipients,
wherein the obeticholic acid or the pharmaceutically acceptable salt or amino acid conjugate thereof is in the form of jet-milled particles, and wherein at least 50% of the particles have a diameter of 200 μm or less;
wherein at least one pharmaceutically acceptable excipient in the tablet has an alcohol content of less than about 6% (w/w);
wherein the amount is a starting dose, an adjusted dose or a re-adjusted dose; and
wherein the tablet is administered daily (QD), every other day (Q2D), once a week (QW), twice a week (BID), three times a week (TIW), once a month (QM), or twice a month (Q2M).
24. The method of claim 23 , wherein the intra-granular portion comprises obeticholic acid.
25. The method of claim 24 , wherein the amount is 10 mg, and the tablet is administered daily.
26. The method of claim 24 , wherein the amount is 5 mg, and the tablet is administered daily.
27. The method of claim 24 , wherein the amount is about 1 mg to about 5 mg, and the tablet is administered daily.
28. The method of claim 24 , wherein the method further comprises administering to the subject a bile acid binding resin at least 4 hours before the tablet is administered.
29. The method of claim 24 , wherein the method further comprises administering to the subject a bile acid binding resin at least 4 hours after the tablet is administered.
30. The method of claim 23 , wherein the amount is about 1 mg to about 10 mg.
31. The method of claim 23 , wherein the amount is a starting dose and the tablet is administered in a titration period.
32. The method of claim 31 , wherein the titration period is from 1 month to 6 months.
33. The method of claim 32 , wherein the titration period is 3 months or 6 months.