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 composition comprising obeticholic acid, or a pharmaceutically acceptable salt, ester, or amino acid conjugate thereof, wherein obeticholic acid or a pharmaceutically acceptable salt, ester, or amino acid conjugate thereof is in the form of particles, and wherein at least 50% of the particles have a diameter of 200 μm or less.
2. The composition of claim 1 , wherein at least 50% of the particles have a diameter of 100 μm or less.
3. The composition of claim 2 , wherein at least 50% of the particles have a diameter of 50 μm or less.
4. The composition of claim 3 , wherein at least 50% of the particles have a diameter of 10 μm or less.
5. The composition of claim 4 , wherein at least 50% of the particles have a diameter of 5 μm or less.
6. The composition of claim 1 , wherein at least 90% of the particles have a diameter of 200 μm or less.
7. The composition of claim 6 , wherein at least 90% of the particles have a diameter of 100 μm or less.
8. The composition of claim 7 , wherein at least 90% of the particles have a diameter of 25 μm or less.
9. The composition of claim 1 further comprising at least one pharmaceutically acceptable excipient having an alcohol content of less than about 6% (wt/wt).
10. The composition of claim 9 , wherein the at least one pharmaceutical acceptable excipient is sodium starch glycolate.
11. A tablet comprising an intra-granular portion and an extra-granular portion, the intra-granular portion comprising obeticholic acid, or a pharmaceutically acceptable salt, ester, or amino acid conjugate thereof, microcrystalline cellulose, and one or more additional pharmaceutical excipients, and the extra-granular portion comprising one or more pharmaceutical excipients.
12. The tablet of claim 11 , wherein the extra-granular portion comprises microcrystalline cellulose.
13. A method for preparing a composition comprising obeticholic acid, or a pharmaceutically acceptable salt, ester, or amino acid conjugate thereof, in the form of particles, wherein at least 50% of the particles have a diameter of 200 μm or less, comprising forming the particles through jet-milling.
14. The tablet of claim 11 , wherein obeticholic acid or a pharmaceutically acceptable salt, ester, or amino acid conjugate thereof is jet-milled.
15. The tablet of claim 14 , wherein obeticholic acid or a pharmaceutically acceptable salt, ester, or amino acid conjugate thereof is in the form of particles, and wherein at least 50% of the particles have a diameter of 200 μm or less.
16. The composition of claim 1 is in a unit dosage form.
17. The composition of claim 16 , wherein the unit dosage form is a tablet.
18. The composition of claim 17 , wherein the tablet comprises an intra-granular portion and an extra-granular portion.
19. The composition of claim 18 , wherein the intra-granular portion comprises microcrystalline cellulose and obeticholic acid, or a pharmaceutically acceptable salt, ester, or amino acid conjugate thereof in a ratio between about 20:1 to about 1:5.