Dosage form compositions comprising an inhibitor of bruton's tyrosine kinase

Abstract

The invention relates generally crystalline mesylate salts, crystalline chloride salts and crystalline sulfate salts of the compound (S)-2-(3′-(hydroxymethyl)-1-methyl-5-((5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino)-6-oxo-1,6-dihydro-[3,4′-bipyridin]-2′-yl)-7,7-dimethyl-2,3,4,6,7,8-hexahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one that is an inhibitor of Bruton's tyrosine kinase. In some aspects, the crystalline salts are single polymorphs.

What is claimed is: 
     
         1 . A salt composition comprising:
 (1) a cation formed from a free base of structure (I):   
       
         
           
           
               
               
           
         
         
           and 
         
         (2) an anion selected from mesylate, chloride and sulfate. 
       
     
     
         2 . The composition of  claim 1  wherein the salt is crystalline. 
     
     
         3 . The composition of  claim 2  wherein the salt is the mesylate salt. 
     
     
         4 . The composition of  claim 3  wherein the mesylate salt is a type A polymorph having an XRPD pattern comprising at least three characteristic peaks selected from peaks with 2θ angle degrees±0.2 2θ angle degrees of about 3.78, about 6.48, about 7.91, about 9.92, about 11.89, about 14.26, about 15.12, about 15.89, about 17.24, about 18.10, about 19.86, about 20.55 and about 21.41. 
     
     
         5 . The composition of  claim 3  wherein at least 50 percent by weight of the mesylate salt dissolves in a pH 4.5 aqueous medium at 37° C. in 10 minutes and wherein at least 80 percent by weight of the mesylate salt dissolves in the pH 4.5 aqueous medium at 37° C. in 30 minutes. 
     
     
         6 . The composition of  claim 2  wherein the salt is the chloride salt. 
     
     
         7 . The composition of  claim 6  wherein chloride salt is a type A polymorph having an XRPD pattern comprising at least three characteristic peaks selected from peaks with 2θ angle degrees±0.2 2θ angle degrees of about 3.97, about 6.83, about 7.92, about 10.46, about 11.87, about 14.21, about 15.79 and about 19.76. 
     
     
         8 . The composition of  claim 2  wherein the salt is the sulfate salt. 
     
     
         9 . The composition of  claim 8  wherein sulfate salt is a type A polymorph having an XRPD pattern comprising at least three characteristic peaks selected from selected from peaks with 2θ angle degrees±0.2 2θ angle degrees of about 3.72, about 5.17, about 10.34, about 11.53, about 13.76, about 14.71, about 15.06, about 16.29, about 18.28 and about 19.74.