Solid state forms of venetoclax and processes for preparation of venetoclax

Abstract

Solid state forms of Venetoclax, pharmaceutical compositions thereof, and uses thereof are disclosed. Also disclosed are processes for the preparation of Venetoclax.

1 . A crystalline form of Venetoclax, designated Form 5, which is characterized by:
 a. an XRPD pattern having peaks at 5.2, 10.4, 11.4, 13.8 and 15.2 degrees 2-theta±0.2 degrees 2-theta;   b. an XRPD pattern as depicted in  FIG. 6 ; or   c. a combination of a. and b.   
     
     
         2 . A crystalline form according to  claim 1 , designated Form 5, which is characterized by the XRPD pattern having peaks at 5.2, 10.4, 11.4, 13.8 and 15.2 degrees 2-theta±0.2 degrees 2-theta, and also having one, two, three or four additional peaks selected from 9.1, 14.3, 19.7, 21.8 and 22.8 degrees two theta±0.2 degrees two theta. 
     
     
         3 . A crystalline form according to  claim 1 , designated Form 5, wherein the form is anhydrous. 
     
     
         4 . A crystalline form according to  claim 1 , designated Form 5, which contains: no more than about 20% of any other crystalline forms of venetoclax. 
     
     
         5 . A crystalline form according to  claim 1 , designated Form 5, which contains: no more than about 10% of any other crystalline forms of venetoclax. 
     
     
         6 . A crystalline form according to  claim 1 , designated Form 5, which contains: no more than about 5% of any other crystalline forms of venetoclax. 
     
     
         7 . A crystalline form according to  claim 1 , designated Form 5, which contains: no more than about 2% of any other crystalline forms of venetoclax. 
     
     
         8 . A crystalline form according to  claim 1 , designated Form 5, which contains: no more than about 1% of any other crystalline forms of venetoclax. 
     
     
         9 . A crystalline form according to  claim 1 , designated Form 5, which contains: about 0% of any other crystalline forms of venetoclax. 
     
     
         10 . A crystalline form according to  claim 1 , designated Form 5, which contains: no more than about 20% of amorphous venetoclax. 
     
     
         11 . A crystalline form according to  claim 1 , designated Form 5, which contains: no more than about 10% of amorphous venetoclax. 
     
     
         12 . A crystalline form according to  claim 1 , designated Form 5, which contains: no more than about 5% of amorphous venetoclax. 
     
     
         13 . A crystalline form according to  claim 1 , designated Form 5, which contains: no more than about 2% of amorphous venetoclax. 
     
     
         14 . A crystalline form according to  claim 1 , designated Form 5, which contains: no more than about 1% of amorphous venetoclax. 
     
     
         15 . A crystalline form according to  claim 1 , designated Form 5, which contains: about 0% of amorphous venetoclax. 
     
     
         16 . A pharmaceutical composition, comprising:
 a crystalline form of Venetoclax, designated Form 5, which is characterized by:
 a. an XRPD pattern having peaks at 5.2, 10.4, 11.4, 13.8 and 15.2 degrees 2-theta±0.2 degrees 2-theta; 
 b. an XRPD pattern as depicted in  FIG. 6 ; or 
 c. a combination of a. and b.; and 
   at least one pharmaceutically acceptable excipient.   
     
     
         17 . A method of treating chronic lymphocytic leukemia, comprising:
 administering a therapeutically effective amount of a crystalline form of Venetoclax, designated Form 5 to a subject in need thereof;   wherein Venetoclax Form 5 is characterized by:
 a. an XRPD pattern having peaks at 5.2, 10.4, 11.4, 13.8 and 15.2 degrees 2-theta±0.2 degrees 2-theta; 
 b. an XRPD pattern as depicted in  FIG. 6 ; or 
 c. a combination of a. and b. 
   
     
     
         18 . A method of preparing a venetoclax solid dispersion or premix, the method comprising:
 mixing a crystalline form of venetoclax according to  claim 1 , with a pharmaceutically acceptable carrier, and optionally at least one other pharmaceutically acceptable excipient in a solvent to provide a mixture; and   removing the solvent from the mixture thereby forming the venetoclax solid dispersion or premix.   
     
     
         19 . The method of  claim 18 , wherein the pharmaceutically acceptable carrier comprises at least one of copovidone or povidone. 
     
     
         20 . A method of preparing an amorphous venetoclax, the method comprising:
 dissolving a crystalline form of venetoclax according to  claim 1  in a solvent to provide a solution; and   precipitating the amorphous venetoclax from the solution or removing the solvent from the solution to form the amorphous venetoclax.   
     
     
         21 . A method comprising:
 converting the crystalline form of venetoclax according to  claim 1  to another solid state form of venetoclax or to a pharmaceutically acceptable salt of venetoclax.