Single morphic forms of metalloproteinase inhibitors

Abstract

The present invention pertains to single morphic forms of a compound selected from 2S-[4-(2,5-dioxopyrrolidin-1-yl)-2S-mercaptobutyrylamino]4-methylpentanoic acid (2,2-dimethyl-1S-methylcarbamoylpropyl)amide and 2S-[2S-mercapto-4-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)butyrylamino]-4-methylpentanoic acid (2,2-dimethyl-1S-methylcarbamoylpropyl)amide, isolable as such.

1 . A single morphic form of a compound selected from the group consisting of 2S-[4-(2,5-dioxopyrrolidin-1-yl)-2S-mercaptobutyrylamino]-4-methylpentanoic acid (2,2-dimethyl-1S-methylcarbamoylpropyl)amide and 2S-[2S-mercapto-4-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)butyrylamino]-4-methylpentanoic acid (2,2-dimethyl-1S-methylcarbamoylpropyl)amide, isolable as such.  
     
     
         2 . The single morphic form according to  claim 1 , which is non-hygroscopic.  
     
     
         3 . The single morphic form according to  claim 1 , which is solvent-free.  
     
     
         4 . The single morphic form of the first compound according to  claim 1 , having peaks at 8.0, 9.1, 10.7, 12.4, 13.6 and 17.0, by X-ray powder diffraction.  
     
     
         5 . The single morphic form of the second compound according to  claim 1 , having peaks at 7.6, 8.0, 15.3, 16.1, 16.5 and 17.8, by X-ray powder diffraction.  
     
     
         6 . A pharmaceutical unit dosage form comprising a single morphic form according to  claim 1 , obtainable by milling, and a pharmaceutically-acceptable carrier.  
     
     
         7 . The dosage form according to  claim 6 , which is a filled capsule.  
     
     
         8 . The dosage form according to  claim 6 , which is a compressed tablet.  
     
     
         9 . A method for the manufacture of a dosage form according to  claim 6 , which comprises milling the morphic form, mixing it with the carrier, and optionally also compressing the mixture, wherein the structure of the morphic form is unchanged by the method.  
     
     
         10 . The method for the manufacture of a dosage form according to  claim 9 , wherein the dosage form is a filled capsule.  
     
     
         11 . The method for the manufacture of a dosage form according to  claim 9 , wherein the dosage form is a compressed tablet.  
     
     
         12 . The single morphic form according to  claim 2 , which is solvent free.