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 pharmaceutical composition comprising an active pharmaceutical ingredient, which is obeticholic acid or a pharmaceutically acceptable salt or amino acid conjugate thereof, and one or more pharmaceutically acceptable excipients,
 which provides a peak plasma concentration (C max ) of obeticholic acid in a subject at a median time (T max ) of approximately 1.5 hours after administration of the pharmaceutical composition to the subject.   
     
     
         2 . The pharmaceutical composition of  claim 1 , which provides formation of glyco-obeticholic acid and/or tauro-obeticholic acid after the administration of the pharmaceutical composition to the subject and which provides a peak plasma concentration (C max ) of glyco-obeticholic acid or of tauro-obeticholic acid at a median time (T max ) of approximately 10 hours after the administration. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein said one or more pharmaceutically acceptable excipients have a total alcohol impurity having a primary alcohol group content of less than about 6% (wt/wt). 
     
     
         4 . The pharmaceutical composition of  claim 3 , wherein said one or more pharmaceutically acceptable excipients having a total alcohol impurity having a primary alcohol group content of less than about 6% (wt/wt) is sodium starch glycolate. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the active pharmaceutical ingredient is obeticholic acid. 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the obeticholic acid is present in an amount of 5 mg or 10 mg. 
     
     
         7 . The pharmaceutical composition of  claim 6 , wherein the obeticholic acid is present in an amount of 10 mg. 
     
     
         8 . The pharmaceutical composition of  claim 1 , in the form of an oral dosage form. 
     
     
         9 . The pharmaceutical composition of  claim 7 , wherein the oral dosage form is a tablet. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the active pharmaceutical ingredient is the only active pharmaceutical ingredient in the pharmaceutical composition. 
     
     
         11 . A method of treating primary biliary cholangitis (PBC), comprising administering to a subject the pharmaceutical composition of  claim 1 . 
     
     
         12 . The method of  claim 11 , wherein the active pharmaceutical ingredient is obeticholic acid. 
     
     
         13 . The method of  claim 12 , wherein the obeticholic acid is present in an amount of 10 mg. 
     
     
         14 . The method of  claim 11 , wherein the active pharmaceutical ingredient is the only active pharmaceutical ingredient in the pharmaceutical composition.