Salts and polymorphs of 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6h-azepino[5,4,3-cd]indol-6-one

Abstract

The present invention relates to novel polymorphic forms of 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one, and to processes for their preparation. Such polymorphic forms may be a component of a pharmaceutical composition and may be used to treat a mammalian disease condition mediated by poly(ADP-ribose) polymerase activity including the disease condition such as cancer.

1 - 7 . (canceled) 
     
     
         8 . A process for preparing a solid dosage form containing a camsylate salt of 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one, comprising
 i) preparing a first vessel comprising 8-fluoro-2-{4-[(methylamino)methyl] phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one and a first solvent comprising one or more of water, an alcohol, and an ether;   ii) preparing a second vessel comprising camphor sulfonic acid and a second solvent comprising one or more of water, an alcohol, and an ether;   iii) combining the contents of the first vessel and the second vessel to form a camsylate salt of 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one; and   iv) isolating the camsylate salt formed in step iii);   v) combining the isolated camsylate salt with one or more of a pharmaceutically acceptable carrier, a pharmaceutically acceptable diluent, a pharmaceutically acceptable vehicle, or a pharmaceutically acceptable excipient; and   vi) preparing the solid dosage form by one or more processes selected from mixing, granulating, and compressing.   
     
     
         9 . The process of  claim 8  wherein the camphor sulfonic acid is S-camphor sulfonic acid. 
     
     
         10 . The process of  claim 8  wherein the camphor sulfonic acid is R-camphor sulfonic acid. 
     
     
         11 . The process of  claim 8  wherein the camphor sulfonic acid comprises a ratio of R-camphor sulfonic acid and S-camphor sulfonic acid. 
     
     
         12 . The process of  claim 11  wherein the camphor sulfonic acid is selected from 1R:1S-camphor sulfonic acid, 1R:9S-camphor sulfonic acid, 1R:3S-camphor sulfonic acid, and 1R:7S-camphor sulfonic acid. 
     
     
         13 . The process of  claim 12  wherein the camphor sulfonic acid is 1R:1S-camphor sulfonic acid. 
     
     
         14 . The process of  claim 8  wherein the isolated camsylate salt is amorphous. 
     
     
         15 . The process of  claim 8  wherein the isolated camsylate salt is crystalline. 
     
     
         16 . The process of  claim 15  wherein the isolated camsylate salt is crystalline polymorph Form A. 
     
     
         17 . The process of  claim 16  wherein the isolated camsylate salt is crystalline S-camsylate polymorph Form A. 
     
     
         18 . The process of  claim 8  wherein the solid dosage form is selected from tablets, capsules, troches, and lozenges. 
     
     
         19 . The process of  claim 18  wherein the solid dosage form is a tablet. 
     
     
         20 . The process of  claim 8  wherein combining the isolated camsylate salt with one or more of a pharmaceutically acceptable carrier, a pharmaceutically acceptable diluent, a pharmaceutically acceptable vehicle, or a pharmaceutically acceptable excipient in step v) produces a mixture, and step vi) comprises granulating the mixture to form granules and processing the granules to prepare the solid dosage form. 
     
     
         21 . The process of  claim 8  wherein the first solvent comprises one or more of water, tetrahydrofuran, and isopropyl alcohol. 
     
     
         22 . The process of  claim 8  wherein the second solvent comprises one or more of water, tetrahydrofuran, and isopropyl alcohol. 
     
     
         23 . The process of  claim 8  wherein the first solvent comprises isopropyl alcohol and the second solvent comprises isopropyl alcohol. 
     
     
         24 . The process of  claim 8 , wherein the contents of the first vessel and the second vessel are heated after they are combined in step iii). 
     
     
         25 . The process of  claim 8  wherein isolating the camsylate salt in step iv) comprises filtration. 
     
     
         26 . The process of  claim 25  wherein the isolated camsylate salt in step iv) is washed with a solvent comprising one or more of water and an alcohol. 
     
     
         27 . The process of  claim 8  wherein isolating the camsylate salt in step iv) comprises crystallization.