Pharmaceutical Composition

Abstract

The present invention relates to a pharmaceutical composition for oral administration comprising a non-bile farnesoid X receptor (FXR) agonist 2-[(1R,3R,5S)-3-({5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid, or a pharmaceutically acceptable salt thereof, and at least one lipid excipient; to a capsule for oral administration comprising said pharmaceutical composition; to the use of said pharmaceutical composition for the treatment of a FXR mediated disorder or condition; and to a process for preparing said pharmaceutical composition.

1 . A pharmaceutical composition for oral administration comprising 2-[(1R,3R,5S)-3-({5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid and at least one lipid excipient selected from glycerol mono/dicaprylate, glyceryl caprylate/caprate, propylene glycol monolaurate, or mixtures thereof. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein said composition comprises about 1 to 250 μg of 2-[(1R,3R,5S)-3-({5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein said composition optionally comprises a surfactant. 
     
     
         4 . The pharmaceutical composition according to  claim 3 , wherein the surfactant is selected from polyoxyethylene (25)-glyceryl trioleate, polyoxyethylene (20) glyceryl trioleate, polyoxyethylene (20) sorbitan trioleate, caprylic/capric triglyceride, or mixtures thereof. 
     
     
         5 . The pharmaceutical composition according to  claim 3 , wherein said surfactant is selected from polyoxyl 40 hydrogenated castor oil, polyoxyl 60 hydrogenated castor oil, alkyl ether ethoxylate, cetostearyl alcohol ethoxylate, polyethylene glycosylated mixed glycerides, macrogolglycerol ricinoleate, polysorbates, sorbitan trioleate, or mixtures thereof. 
     
     
         6 . The pharmaceutical composition of  claim 3 , wherein the surfactant comprises caprylic/capric triglyceride. 
     
     
         7 . The pharmaceutical composition of  claim 1 , comprising: (i) about 0.001% to about 0.04% by weight of said composition of 2-[(1R,3R,5S)-3-({5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid or a pharmaceutically acceptable salt thereof; and (ii) a lipid excipient selected from propylene glycol monolaurate and glyceryl caprylate/caprate or mixtures thereof; wherein said composition optionally comprises a surfactant. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein said composition is a liquid solution. 
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein said composition is a capsule. 
     
     
         10 . The pharmaceutical composition of  claim 9 , wherein said capsule is a soft gelatin capsule. 
     
     
         11 . A method for treating a condition mediated by farnesoid X receptor (FXR), comprising administering to a subject in need thereof, said pharmaceutical composition of  claim 1 . 
     
     
         12 . The method of  claim 11 , wherein said condition mediated by FXR is selected from primary biliary cirrhosis (PBC), non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). 
     
     
         13 . A method for treating a condition mediated by farnesoid X receptor (FXR), comprising administering to a subject in need thereof, said pharmaceutical composition of  claim 6 . 
     
     
         14 . The method of  claim 13 , wherein said condition mediated by FXR is selected from primary biliary cirrhosis (PBC), non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).