Solid State Forms Of Cabazitaxel And Processes For Preparation Thereof

Abstract

The invention relates to solid state forms of Cabazitaxel, and processes for preparation, via novel synthetic intermediates, thereof, and formulations comprising one or more of the solid state forms of Cabazitaxel. The present invention further provides pharmaceutical compositions comprising one or more of the solid state forms of Cabazitaxel, and a method of treating hormone-refractory prostate cancer

What is claimed is: 
     
         1 . A process for preparing a cabazitaxel, cabazitaxel salts, or solid state forms thereof, comprising preparing any one or a combination of crystalline cabazitaxel that is:
 crystalline cabazitaxel designated as form III, characterized by:
 a solid state  13 C NMR spectrum with peaks at 139.8 127.8, 63.4, 25.4 and 23.5 ppm±0.2 ppm; 
 a solid state  13 C NMR spectrum having chemical shift differences between said characteristic peaks at 139.8 127.8, 63.4, 25.4 and 23.5 ppm±0.2 ppm and a reference peak at 125.1±0.2 ppm of 14.8, 2.8, −61.7, −99.6 and −101.6 ppm±0.1 ppm, respectively; 
 a solid state  13 C NMR spectrum substantially as depicted in any one of  FIGS. 27-29 ; and combinations thereof; 
   crystalline cabazitaxel designated as form II, characterized by:
 a solid state  13 C NMR spectrum with peaks at 174.3, 170.8, 166.5, 137.7, and 135.9 ppm±0.2 ppm; 
 a solid state  13 C NMR spectrum having chemical shift differences between said characteristic peaks at 174.3, 170.8, 166.5, 137.7, and 135.9 ppm±0.2 ppm and a reference peak at 125.1±0.2 ppm of 49.2, 45.7, 41.4, 12.6 and 10.8 ppm±0.1 ppm, respectively; 
 a solid state  13 C NMR spectrum substantially as depicted in any one of  FIGS. 24-26 ; and combinations thereof; 
   crystalline cabazitaxel form IV, characterized by:
 a solid state  13 C NMR spectrum with peaks at 128.4, 60.6, 19.0 and 13.6 ppm±0.2 ppm; 
 a solid state  13 C NMR spectrum having chemical shift differences between said characteristic peaks at 128.4, 60.6, 19.0 and 13.6 ppm±0.2 ppm and a reference peak at 125.2±0.2 ppm of 3.2, −64.7, −106.2 and −111.6 ppm±0.1 ppm, respectively; 
 a solid state  13 C NMR spectrum substantially as depicted in any one of  FIGS. 30-32 ; and combinations thereof; or 
   crystalline cabazitaxel form V, characterized by:
 a solid state  13 C NMR spectrum with peaks at 135.5, 70.4, 25.7 and 10.6 ppm±0.2 ppm; 
 a solid state  13 C NMR spectrum having chemical shift differences between said characteristic peaks at 135.5, 70.4, 25.7 and 10.6 ppm±0.2 ppm and a reference peak at 125.1±0.2 ppm of 10.4, −54.7, −99.4 and −114.5 ppm±0.1 ppm, respectively; 
 a solid state  13 C NMR pattern substantially as depicted in any one of  FIGS. 33-35 ; and combinations thereof; 
   
       and converting said one or combination of one or a combination of crystalline or amorphous cabazitaxel to cabazitaxel, cabazitaxel salts, or solid state forms thereof. 
     
     
         2 . A process for preparing a cabazitaxel, cabazitaxel salts, or solid state forms thereof, comprising preparing any one or a combination of a crystalline cabazitaxel that is:
 crystalline cabazitaxel form III 2-propanol solvate, characterized: a powder X-ray diffraction pattern having peaks at 7.4, 9.0, 10.3, 13.3 and 13.6 degrees two theta±0.1 degrees two theta and optionally having no peak in the area from 10.5 to 12.1 degrees two theta;   crystalline cabazitaxel form II MTBE solvate, characterized by: a powder X-ray diffraction pattern having peaks at 7.4, 7.7, 8.9, 12.1 and 13.2 degrees two theta±0.1 degrees two theta and optionally having no peak in the area from 10.4 to 11.9 degrees two theta;   crystalline cabazitaxel form IV n-butanol solvate, characterized by: a powder X-ray diffraction pattern having peaks at 7.4, 7.9, 8.8, 12.9 and 13.5 degrees two theta±0.1 degrees two theta and optionally having no peak in the area from 10.4 to 12.2 degrees two theta; or   crystalline cabazitaxel form V 1-propanol solvate characterized by: a powder X-ray diffraction pattern having peaks at 7.8, 9.0, 10.2, 15.1 and 15.3 degrees two theta±0.1 degrees two theta and optionally having no peak in the area from 10.5 to 12.1 degrees two theta   
       and converting said one or combination of one or a combination of crystalline or amorphous cabazitaxel to cabazitaxel, cabazitaxel salts, or solid state forms thereof. 
     
     
         3 . Amorphous cabazitaxel in a powdery, non-foamy form. 
     
     
         4 . A process for preparing a cabazitaxel, cabazitaxel salts, or solid state forms thereof, comprising preparing an amorphous cabazitaxel according to  claim 3 , and converting said one or combination of one or a combination of crystalline or amorphous cabazitaxel to cabazitaxel, cabazitaxel salts, or solid state forms thereof.