Solid state forms of vemurafenib hydrochloride

Abstract

Provided herein are solid state forms of Vemurafenib hydrochloride, processes for preparing the solid state forms, as well as pharmaceutical compositions and formulations comprising said solid state forms.

1 - 16 . (canceled) 
     
     
         17 . A method of treating a subject suffering from cancer comprising administering to the subject a therapeutically effective amount of a crystalline form of Vemurafenib hydrochloride salt, designated as Form II, characterized by one or more of the following:
 a powder X-ray diffraction pattern having peaks at 5.0, 9.9, 15.7, 19.8 and 22.1 degrees two theta±0.2 degrees two theta;   a powder X-ray diffraction pattern substantially as depicted in  FIG. 1 ;   a solid-state  13 C NMR spectrum having characteristic peaks at 51.0, 114.5, 132.3, 138.0 and 139.5 ppm, ±0.2 ppm;   a solid state  13 C NMR spectrum having chemical shift differences between said characteristic peaks and a peak at 120.9 ppm±0.2 ppm of −69.9, −6.4, 11.4, 17.1 and 18.6±0.1 ppm, respectively;   a solid state  13 C NMR spectrum substantially as shown in  FIG. 3 ;   or any combination of these data.   
     
     
         18 . The method of  claim 17 , wherein the cancer is metastatic melanoma. 
     
     
         19 . The method of  claim 18 , wherein the metastatic melanoma has a BRAF V600E mutation. 
     
     
         20 . A process for preparing a pharmaceutical formulation comprising a crystalline form of Vemurafenib hydrochloride salt, designated as Form II, characterized by one or more of the following:
 a powder X-ray diffraction pattern having peaks at 5.0, 9.9, 15.7, 19.8 and 22.1 degrees two theta±0.2 degrees two theta;   a powder X-ray diffraction pattern substantially as depicted in  FIG. 1 ;   a solid-state  13 C NMR spectrum having characteristic peaks at 51.0, 114.5, 132.3, 138.0 and 139.5 ppm, ±0.2 ppm;   a solid state  13 C NMR spectrum having chemical shift differences between said characteristic peaks and a peak at 120.9 ppm±0.2 ppm of −69.9, −6.4, 11.4, 17.1 and 18.6±0.1 ppm, respectively;   a solid state  13 C NMR spectrum substantially as shown in  FIG. 3 ;   or any combination of these data;   comprising:   combining the crystalline form of Vemurafenib hydrochloride with at least one pharmaceutically acceptable excipient.   
     
     
         21 . A process for preparing Vemurafenib comprising
 preparing a crystalline form of Vemurafenib hydrochloride salt, designated as Form II, characterized by one or more of the following:   a powder X-ray diffraction pattern having peaks at 5.0, 9.9, 15.7, 19.8 and 22.1 degrees two theta±0.2 degrees two theta;   a powder X-ray diffraction pattern substantially as depicted in  FIG. 1 ;   a solid-state  13 C NMR spectrum having characteristic peaks at 51.0, 114.5, 132.3, 138.0 and 139.5 ppm, ±0.2 ppm;   a solid state  13 C NMR spectrum having chemical shift differences between said characteristic peaks and a peak at 120.9 ppm±0.2 ppm of −69.9, −6.4, 11.4, 17.1 and 18.6±0.1 ppm, respectively;   a solid state  13 C NMR spectrum substantially as shown in  FIG. 3 ;   or any combination of these data; and   converting the crystalline form of Vemurafenib hydrochloride to Vemurafenib.   
     
     
         22 . The process according to  claim 21 , wherein the conversion is accomplished by a process comprising basifying the crystalline form of Vemurafenib hydrochloride to obtain the Vemurafenib. 
     
     
         23 . A process for preparing a Vemurafenib salt comprising:
 preparing a crystalline form of Vemurafenib hydrochloride salt, designated as Form II, characterized by one or more of the following:   a powder X-ray diffraction pattern having peaks at 5.0, 9.9, 15.7, 19.8 and 22.1 degrees two theta±0.2 degrees two theta;   a powder X-ray diffraction pattern substantially as depicted in  FIG. 1 ;   a solid-state  13 C NMR spectrum having characteristic peaks at 51.0, 114.5, 132.3, 138.0 and 139.5 ppm, ±0.2 ppm;   a solid state  13 C NMR spectrum having chemical shift differences between said characteristic peaks and a peak at 120.9 ppm±0.2 ppm of −69.9, −6.4, 11.4, 17.1 and 18.6±0.1 ppm, respectively;   a solid state  13 C NMR spectrum substantially as shown in  FIG. 3 ;   or any combination of these data; and   converting the crystalline form of Vemurafenib hydrochloride to the Vemurafenib salt.   
     
     
         24 . The process according to  claim 23 , wherein the conversion is accomplished by a process comprising basifying the crystalline form of Vemurafenib hydrochloride to obtain Vemurafenib and adding an acid or a base to obtain the Vemurafenib salt.