Solid state forms of a potent hcv inhibitor

Abstract

This invention relates to novel sodium salt forms of the following Compound (1), and methods for the preparation thereof, pharmaceutical compositions thereof, and their use in the treatment of Hepatitis C Viral (HCV) infection:

1 . A crystalline sodium salt of the compound of the following formula (1): 
       
         
           
           
               
               
           
         
       
     
     
         2 . A process for preparing a crystalline sodium salt according to  claim 1 , said process comprising the following steps:
 (a) reacting Compound (1) with an aqueous NaOH solution in a suitable solvent to form a clear solution;   (b) adding methyl ethylketone to the mixture obtained in step (a) while heating the mixture to a temperature of about 50-60° C.;   (c) optionally, adding Compound (1) sodium salt methyl ethylketone solvate seeds to the mixture obtained in step (b) at about 50° C.;   (d) adding additional methyl ethylketone to the mixture obtained in step (b) or (c) at about 50° C.; and   (e) cooling the mixture obtained in step (d) to about 25° C., resulting in precipitation of Compound (1) sodium salt crystals.   
     
     
         3 . A pharmaceutical composition comprising a crystalline sodium salt according to  claim 1  and at least one pharmaceutically acceptable carrier or diluent. 
     
     
         4 . A pharmaceutical composition according to  claim 3  comprising:
 (a) Compound (1) crystalline sodium salt; 
 (b) at least one surfactant; 
 (c) at least one basifier; 
 
       and optionally one or more pharmaceutically acceptable excipients. 
     
     
         5 . A pharmaceutical composition according to  claim 3  comprising:
 (a) about 5 to 60% by weight of Compound (1) crystalline sodium salt; 
 (b) about 1 to 10% by weight surfactant; 
 (c) about 2 to 20% by weight basifier; 
 (d) 0 to about 40% by weight binder; 
 and optionally one or more pharmaceutically acceptable excipients. 
 
     
     
         6 . A pharmaceutical composition according to  claim 3  comprising:
 (a) about 10 to 50% by weight Compound (1) crystalline sodium salt; 
 (b) about 2 to 8% by weight surfactant; 
 (c) about 4 to 16% by weight basifier; 
 (d) about 1 to 25% by weight binder; 
 and optionally one or more pharmaceutically acceptable excipients. 
 
     
     
         7 . A pharmaceutical composition according to  claim 3  comprising:
 (a) about 20 to 50% by weight Compound (1) crystalline sodium salt; 
 (b) about 2 to 6% by weight surfactant; 
 (c) about 4 to 12% by weight basifier; 
 (d) about 5 to 20% by weight binder;
 and optionally one or more pharmaceutically acceptable excipients. 
 
 
     
     
         8 . A sodium salt of the compound of the following formula (1) in amorphous form: 
       
         
           
           
               
               
           
         
       
     
     
         9 . A pharmaceutical composition comprising the amorphous Compound (1) sodium salt according to  claim 8  and at least one pharmaceutically acceptable carrier or diluent. 
     
     
         10 . A pharmaceutical composition according to  claim 9  comprising
 (a) amorphous Compound (1) sodium salt; 
 (b) at least one surfactant; 
 (c) at least one basifier; 
 (d) at least one polymer; 
 
       and optionally one or more pharmaceutically acceptable excipients. 
     
     
         11 . A pharmaceutical composition according to  claim 9  comprising:
 (a) 1% to 90% by weight amorphous Compound (1) sodium salt; 
 (b) 1% to 50% by weight surfactant; 
 (c) 1% to 50% by weight basifier; 
 (d) 1% to 99% by weight polymer; 
 
       and optionally one or more pharmaceutically acceptable excipients. 
     
     
         12 . A pharmaceutical composition according to  claim 9  comprising:
 (a) 1% to 80% by weight amorphous Compound (1) sodium salt; 
 (b) 1% to 30% by weight surfactant; 
 (c) 2% to 40% by weight basifier; 
 (d) 10% to 80% by weight polymer; 
 
       and optionally one or more pharmaceutically acceptable excipients. 
     
     
         13 . A pharmaceutical composition according to  claim 9  comprising:
 (a) 1% to 70% by weight amorphous Compound (1) sodium salt; 
 (b) 2% to 20% by weight surfactant; 
 (c) 5% to 20% by weight basifier; 
 (d) 20% to 70% by weight polymer; 
 
       and optionally one or more pharmaceutically acceptable excipients. 
     
     
         14 . A pharmaceutical composition according to  claim 9  comprising:
 (a) 30% to 60% by weight amorphous Compound (1) sodium salt; 
 (b) 2% to 10% by weight surfactant; 
 (c) 5% to 15% by weight basifier; 
 (d) 20% to 40% by weight polymer; 
 
       and optionally one or more pharmaceutically acceptable excipients.