Compositions of obeticholic acid and methods of use

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.

1 . A method of treating primary biliary cholangitis (PBC) in a patient in need thereof, said method comprising administering to the patient 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 in an amount of about 1 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 can be 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 tablet comprises obeticholic acid. 
     
     
         4 . The method of  claim 1  wherein the starting dose is administered in a titration period. 
     
     
         5 . The method of  claim 4 , wherein the titration period comprises 1 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 a bile acid binding resin at least 4 hours before administration of the composition. 
     
     
         11 . The use of  claim 1 , wherein the method further comprises administering a bile acid binding resin at least 4 hours after administration of the composition. 
     
     
         12 . A method of treating primary biliary cholangitis (PBC) in a patient in need thereof, said method comprising administering to the patient a tablet comprising obeticholic acid or a pharmaceutically acceptable salt, ester, or amino acid conjugate thereof in an amount of about 1 to about 50 mg, and one or more pharmaceutically acceptable excipients,
 wherein the obeticholic acid or the 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;   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 can be 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 starting dose is administered in a titration period. 
     
     
         16 . The method of  claim 15 , wherein said titration period comprises 1 to 6 months. 
     
     
         17 . The method of  claim 16 , wherein said 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 a bile acid binding resin at least 4 hours before administration of the composition. 
     
     
         22 . The use of  claim 12 , wherein the method further comprises administering a bile acid binding resin at least 4 hours after administration of the composition. 
     
     
         23 . A method of treating primary biliary cholangitis (PBC) in a patient in need thereof, said method comprising administering to the patient 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 in an amount of about 1 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, 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;   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 can be 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 amount is 10 mg, and the tablet is administered daily.