Forms of lapatinib ditosylate and processes for preparation thereof

Abstract

The present invention provides novel polymorphs of lapatinib ditosylate, processes for preparing them, and pharmaceutical compositions comprising one or more of these polymorphs.

1 .- 10 . (canceled) 
     
     
         11 . A process for preparing crystalline form of lapatinib ditosylate (Form XV) characterized by data selected from the group consisting of: a PXRD pattern having peaks at about 6.2, 7.0, 8.9, 12.9, and 16.1±0.2 degrees 2-theta, and a PXRD pattern having peaks at about 6.2, 7.0, 8.9, 12.9, 16.1, 17.0, 18.9, 19.9, 23.7 and 26.0±0.2 degrees 2-theta, the process comprising drying crystalline lapatinib ditosylate Form VI. 
     
     
         12 . A crystalline form of lapatinib ditosylate (Form XV) characterized by data selected from the group consisting of: a PXRD pattern having peaks at about 6.2, 7.0, 8.9, 12.9, and 16.1±0.2 degrees 2-theta; a PXRD pattern having peaks at about 6.2, 7.0, 8.9, 12.9, 16.1, 17.0, 18.9, 19.9, 23.7 and 26.0±0.2 degrees 2-theta; a solid-state  13 C NMR spectrum having signals at about 125.1, 128.3 and 137.1±0.2 ppm; and a solid-state  13 C NMR spectrum having chemical shifts differences between the signal exhibiting the lowest chemical shift and another in the chemical shift range of 100 to 180 ppm of about 17.2, 20.3 and 29.2±0.1 ppm, wherein the signal exhibiting the lowest chemical shift in the chemical shift area of 110 to 180 ppm is typically at about 107.9±1 ppm. 
     
     
         13 . The crystalline form of lapatinib ditosylate of  claim 12 , characterized by a PXRD pattern having peaks at about 6.2, 7.0, 8.9, 12.9, and 16.1±0.2 degrees 2-theta. 
     
     
         14 . The crystalline form of lapatinib ditosylate of  claim 12 , characterized by a PXRD pattern having peaks at about 6.2, 7.0, 8.9, 12.9, 16.1, 17.0, 18.9, 19.9, 23.7 and 26.0±0.2 degrees 2-theta. 
     
     
         15 . The crystalline form of lapatinib ditosylate of  claim 12 , having an X-ray diffraction diagram substantially as depicted in  FIG. 32 . 
     
     
         16 . The crystalline form of lapatinib ditosylate of  claim 12 , wherein it is substantially free of any other polymorphic forms. 
     
     
         17 . A process for preparing the crystalline form of lapatinib ditosylate of  claim 12  comprising drying lapatinib ditosylate Form VI. 
     
     
         18 . The process of  claim 17 , wherein the lapatinib ditosylate Form VI is prepared by a process comprising forming a solution of lapatinib base in dimethylformamide; and adding p-toluenesulfonic acid. 
     
     
         19 . The process of  claim 17 , wherein the lapatinib ditosylate Form VI is dried at about 70° C. to about 90° C., under reduced pressure. 
     
     
         20 . A process for preparing the crystalline form of lapatinib ditosylate of  claim 12  comprising forming a solution of lapatinib ditosylate in dimethylformamide; and adding heptane. 
     
     
         21 . The process of  claim 20 , wherein the lapatinib ditosylate is prepared in situ by a process comprising combining lapatinib base and p-toluenesulfonic acid in dimethylformamide. 
     
     
         22 .- 82 . (canceled) 
     
     
         83 . A pharmaceutical composition comprising the crystalline lapatinib ditosylate of  claim 12 .