Solid state forms of trisodium valsartan: sacubitril

Abstract

Solid state forms of trisodium valsartan:sacubitril, processes for their preparation, pharmaceutical compositions containing such solid state forms and treatment methods using the pharmaceutical compositions are described.

1 . Crystalline form II of trisodium valsartan:sacubitril characterized by
 an X-ray powder diffraction pattern having peaks at: 7.3, 9.4, and 16.5 degrees two theta±0.2 degrees two theta and an absence of a peak at 12.4 degrees two theta±0.2 degrees two theta;   or   an X-ray powder diffraction pattern having peaks at: 5.8, 7.3, 12.9, 15.9, 16.5 and 18.6 degrees two theta±0.2 degrees two theta and an absence of a peak at 12.4 degrees two theta±0.2 degrees two theta.   
     
     
         2 . The crystalline form of  claim 1 , characterized by an X-ray powder diffraction pattern having peaks at: 7.3, 9.4, and 16.5 degrees two theta±0.2 degrees two theta and further characterized by an X-ray powder diffraction pattern having one or more additional peaks selected from: 5.8, 10.9, 12.9, 14.7, 15.9, and 18.6 degrees two theta±0.2 degrees two theta. 
     
     
         3 . The crystalline form of  claim 1 , characterized by an X-ray powder diffraction pattern having peaks at: 7.3, 9.4, and 16.5 degrees two theta±0.2 degrees two theta and further characterized by an X-ray powder diffraction pattern having one or more additional peaks selected from: 4.3, 5.8, 10.0, 10.9, 12.9, 14.7, 15.9, and 18.6 degrees two theta±0.2 degrees two theta. 
     
     
         4 . The crystalline form of  claim 1 , characterized by an X-ray powder diffraction pattern having peaks at: 7.3, 9.4, and 16.5 degrees two theta±0.2 degrees two theta and further characterized by an X-ray powder diffraction pattern having one or more additional peaks selected from: 4.3, 5.0, 5.5, 5.8, 8.5, 8.9, 10.0, 10.9, 11.6, 12.9, 13.7, 13.9, 14.7, 14.8, 15.1, 15.3, 15.9, 17.3, 17.6, 18.6, 19.1, 19.5, 20.3, 21.2, 21.9 and 23.1 degrees two theta±0.2 degrees two theta. 
     
     
         5 . The crystalline form of  claim 1 , characterized by an X-ray powder diffraction pattern having peaks at: 5.8, 7.3, 12.9, 15.9, 16.5 and 18.6 degrees two theta±0.2 degrees two theta and further characterized by an X-ray powder diffraction pattern having one or more additional peaks selected from: 4.3, 9.4, 10.0, 10.9 and 14.7 degrees two theta±0.2 degrees two theta. 
     
     
         6 . The crystalline form of  claim 1 , characterized by an X-ray powder diffraction pattern having peaks at: 5.8, 7.3, 12.9, 15.9, 16.5 and 18.6 degrees two theta±0.2 degrees two theta and further characterized by an X-ray powder diffraction pattern having one or more additional peaks selected from: 4.3, 5.0, 5.5, 8.5, 8.9, 9.4, 10.0, 10.9, 11.6, 13.7, 13.9, 14.7, 14.8, 15.1, 15.3, 17.3, 17.6, 19.1, 19.5, 20.3, 21.2, 21.9 and 23.1 degrees two theta±0.2 degrees two theta. 
     
     
         7 . The crystalline form of  claim 1 , which is a hydrate form. 
     
     
         8 . The crystalline form of  claim 7 , wherein the crystalline form contains from 5.2 to 5.7 wt % water. 
     
     
         9 . The crystalline form of  claim 1 , comprising agglomerates having spherical morphology, wherein at least 50% of the agglomerates have spherical morphology. 
     
     
         10 . The crystalline form of  claim 1 , which contains less than 10% (w/w) of any other forms of trisodium valsartan:sacubitril that is different from crystalline form II. 
     
     
         11 . The crystalline form of  claim 1 , which contains 5% (w/w) or less of any other forms of trisodium valsartan:sacubitril that is different from crystalline form II. 
     
     
         12 . The crystalline form of  claim 1 , which contains 2% (w/w) or less of any other forms of trisodium valsartan:sacubitril that is different from crystalline form II. 
     
     
         13 . Crystalline form II of trisodium valsartan:sacubitril characterized by an X-ray powder diffraction pattern as depicted in  FIG. 1 . 
     
     
         14 . The crystalline form of  claim 13 , further characterized by a DSC as depicted in  FIG. 2 . 
     
     
         15 . A pharmaceutical composition or formulation comprising the crystalline form II of trisodium valsartan:sacubitril as defined in  claim 1  and at least one pharmaceutically acceptable excipient. 
     
     
         16 . A process for preparing a pharmaceutical composition or formulation according  claim 15  comprising combining crystalline form II of trisodium valsartan:sacubitril with at least one pharmaceutically acceptable excipient. 
     
     
         17 . A method of treating hypertension or heart failure in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of crystalline form II of trisodium valsartan:sacubitril as defined in  claim 1 ; or a pharmaceutical formulation comprising the therapeutically amount of crystalline form II of trisodium valsartan:sacubitril as defined in  claim 1  and at least one pharmaceutically acceptable excipient.