Compositions of obeticholic acid and methods of use

Patent metadata

Field	Value
Publication number	US-10052337-B2
Application number	US-201615139138-A
Country	US
Kind code	B2
Filing date	Apr 26, 2016
Priority date	Apr 27, 2015
Publication date	Aug 21, 2018
Grant date	Aug 21, 2018

Abstract

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.

First claim

The invention claimed is:

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.

Assignees

• Intercept Pharmaceuticals Inc
• Sumitomo Dainippon Pharma Co Ltd

Inventors

• Lancaster Richard Gail
• Olmstead Kay K
• Kagihiro Masashi
• Matono Mitsuhiro
• Taoka Ikuko
• Pruzanski Mark
• Shapiro David
• Hooshmand-Rad Roya
• Pencek Richard
• Sciacca Cathi
• Eliot Lise
• Edwards Jeffrey
• Macconell Leigh A
• Marmon Tonya K

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• A61K9/14 Primary

  Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)} · CPC title

• A61K9/2059

  Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin · CPC title