(Z)-2-cyano-3-hydroxy-but-2-enoic acid-(4'-trifluoromethylphenyl)-amide tablet formulations with improved stability

Abstract

The invention relates to solid pharmaceutical compositions comprising (Z)-2-cyano-3-hydroxy-but-2-enoic acid-(4′-trifluoromethylphenyl)-amide, as well as a process for the preparation of the same, methods of using such compositions to treat subjects suffering from autoimmune diseases in particular systemic lupus erythematosus or chronic graft-versus-host disease, multiple sclerosis or rheumatoid arthritis.

1 . (canceled) 
     
     
         2 . A solid pharmaceutical composition comprising a) 1 percent to 30 percent weight:weight teriflunomide, or a pharmaceutically acceptable basic addition salt thereof, b) 5 percent to 20 percent weight:weight disintegrant, c) 0 percent to 40 percent weight:weight binder, d) 0.1 percent to 2 percent weight:weight lubricant, and e) the remaining percentage comprising diluents; wherein the solid pharmaceutical composition contains no more than about 0.5 percent by weight of 2-cyano-N-(4-trifluoromethyl-phenyl)-acetamide. 
     
     
         3 . The solid pharmaceutical composition according to  claim 2 , wherein the solid pharmaceutical composition contains no more than about 0.0863% by weight of 2-cyano-N-(4-trifluoromethyl-phenyl)-acetamide after being stored in an open container at about 40° C. and about 75% relative humidity for about one month. 
     
     
         4 . The solid pharmaceutical composition according to  claim 2 , wherein the solid pharmaceutical composition contains no more than about 0.0353% by weight of 2-cyano-N-(4-trifluoromethyl-phenyl)-acetamide after being stored in a sealed container at about 40° C. and about 75% relative humidity for about one month. 
     
     
         5 . The solid pharmaceutical composition according to  claim 2 , wherein the solid pharmaceutical composition contains no more than about 0.0242% by weight of 2-cyano-N-(4-trifluoromethyl-phenyl)-acetamide after being stored in a sealed container at about 25° C. and about 60% relative humidity for about three months. 
     
     
         6 . The solid pharmaceutical composition according to  claim 2 , wherein the solid pharmaceutical composition contains no more than about 0.0351% by weight of 2-cyano-N-(4-trifluoromethyl-phenyl)-acetamide after being stored in a sealed container at about 30° C. and about 65% relative humidity for about three months. 
     
     
         7 . The solid pharmaceutical composition according to  claim 2 , wherein the solid pharmaceutical composition contains no more than about 0.0807% by weight of 2-cyano-N-(4-trifluoromethyl-phenyl)-acetamide after being stored in a sealed container at about 40° C. and about 75% relative humidity for about three months. 
     
     
         8 . The solid pharmaceutical composition according to  claim 2 , wherein the solid pharmaceutical composition contains no more than about 0.2107% by weight of 2-cyano-N-(4-trifluoromethyl-phenyl)-acetamide after being stored in an open container at about 40° C. and about 75% relative humidity for about three months. 
     
     
         9 . The solid pharmaceutical composition according to  claim 2 , wherein the solid pharmaceutical composition contains no more than about 0.0411% by weight of 2-cyano-N-(4-trifluoromethyl-phenyl)-acetamide after being stored in a sealed container at about 25° C. and about 60% relative humidity for about six months. 
     
     
         10 . The solid pharmaceutical composition according to  claim 2 , wherein the solid pharmaceutical composition contains no more than about 0.0562% by weight of 2-cyano-N-(4-trifluoromethyl-phenyl)-acetamide after being stored in a sealed container at about 30° C. and about 65% relative humidity for about six months. 
     
     
         11 . The solid pharmaceutical composition according to  claim 2 , wherein the solid pharmaceutical composition contains no more than about 0.4447% by weight of 2-cyano-N-(4-trifluoromethyl-phenyl)-acetamide after being stored in an open container at about 40° C. and about 75% relative humidity for about six months. 
     
     
         12 . The solid pharmaceutical composition according to  claim 2 , wherein the solid pharmaceutical composition contains no more than about 0.213% by weight of 2-cyano-N-(4-trifluoromethyl-phenyl)-acetamide after being stored in a sealed container at about 40° C. and about 75% relative humidity for about six months.