Compositions and Formulations of 9-Nitrocamptothecin Polymorphs and Methods of Use Therefor

Abstract

A polymorphic form of 9-nitrocamptothecin is provided, the polymorph being characterizable as having, by differential scanning calorimetry, an endotherm at between 273.9 to 275.9° C., and an exotherm at between 279.3 and 281.3° C.

1 . A polymorphic form of 9-nitrocamptothecin, the polymorph being characterizable as having, by differential scanning calorimetry, an endotherm at between 273.9 to 275.9° C., and an exotherm at between 279.3 and 281.3° C.  
   
   
       2 . A polymorphic form of 9-nitrocamptothecin according to  claim 1 , the polymorph being further characterizable as having, by differential scanning calorimetry, an endotherm at between 274.4 to 275.3° C., and an exotherm at between 279.8 and 280.8° C.  
   
   
       3 . A polymorphic form of 9-nitrocamptothecin according to  claim 1 , the polymorph being further characterizable as having, by differential scanning calorimetry, an endotherm at between 274.7 to 275.1° C., and an exotherm at between 280.1 and 280.5° C.  
   
   
       4 . A polymorphic form of 9-nitrocamptothecin according to  claim 1 , the polymorph being further characterizable as having, by differential scanning calorimetry, an endotherm at between 274.8 to 275.0° C., and an exotherm at between 280.2 and 280.4° C.  
   
   
       5 . A polymorphic form of 9-nitrocamptothecin, the polymorph being characterizable as having, by differential scanning calorimetry, an endotherm at between 273.9 to 275.9° C., and an exotherm at between 279.3 and 281.3° C.  
   
   
       6 . A polymorphic form of 9-nitrocamptothecin, the polymorph being characterizable as having, for Cu Kα radiation of wavelength of 1.5406 Angstrom, an X-ray powder diffraction pattern with diffraction lines at °2θ values 4.8, 14.2, 19.1 and 26.8.  
   
   
       7 . 9-nitrocamptothecin in a form crystallized from acetonitrile.  
   
   
       8 . A polymorphic form of 9-nitrocamptothecin according to  claim 7 , the polymorph being characterizable as having, differential scanning calorimetry, an endotherm at between 273.9 to 275.9° C., and an exotherm at between 279.3 and 281.3° C.  
   
   
       9 . A polymorphic form of 9-nitrocamptothecin according to  claim 7 , the polymorph being characterizable as having an X-ray powder diffraction pattern with diffraction lines at °2θ values 4.8, 14.2, 19.1 and 26.8 for Cu Kα radiation wavelength 1.5406 Angstrom.  
   
   
       10 . A polymorphic form of 9-nitrocamptothecin according to  claim 7 , the polymorph being characterizable as having, for Cu Kα radiation of wavelength 1.5406 Angstrom, an X-ray powder diffraction pattern with diffraction lines at °2θ values 4.8, 14.2, 19.1 and 26.8.  
   
   
       11 . A pharmaceutical composition comprising: 
 a pharmaceutical carrier; and    a polymorphic form of 9-nitrocamptothecin, the polymorph being characterizable as having, by differential scanning calorimetry, an endotherm at between 273.9 to 275.9° C., and an exotherm at between 279.3 and 281.3° C.    
   
   
       12 . A pharmaceutical formulation according to  claim 11 , the polymorph being further characterizable as having, by differential scanning calorimetry, an endotherm at between 274.4 to 275.3° C., and an exotherm at between 279.8 and 280.8° C.  
   
   
       13 . A pharmaceutical formulation according to  claim 11 , the polymorph being further characterizable as having, by differential scanning calorimetry, an endotherm at between 274.7 to 275.1° C., and an exotherm at between 280.1 and 280.5° C.  
   
   
       14 . A pharmaceutical formulation according to  claim 11 , the polymorph being further characterizable as having, by differential scanning calorimetry, an endotherm at between 274.8 to 275.0° C., and an exotherm at between 280.2 and 280.4° C.  
   
   
       15 . A pharmaceutical composition comprising: 
 a pharmaceutical carrier; and    a polymorphic form of 9-nitrocamptothecin, the polymorph being characterizable as having, by differential scanning calorimetry, an endotherm at between 273.9 to 275.9° C., and an exotherm at between 279.3 and 281.3° C.    
   
   
       16 . A pharmaceutical composition comprising: 
 a pharmaceutical carrier; and    a polymorphic form of 9-nitrocamptothecin, the polymorph being characterizable as having, for Cu Kα radiation of wavelength of 1.5406 Angstrom, an X-ray powder diffraction pattern with diffraction lines at °2θ values 4.8, 14.2, 19.1 and 26.8.    
   
   
       17 . A pharmaceutical composition comprising: 
 a pharmaceutical carrier; and    a polymorphic form of 9-nitrocamptothecin crystallized from acetonitrile.    
   
   
       18 . A pharmaceutical formulation according to  claim 17 , the polymorph being characterizable as having, differential scanning calorimetry, an endotherm at between 273.9 to 275.9° C., and an exotherm at between 279.3 and 281.3° C.  
   
   
       19 . A pharmaceutical formulation according to  claim 17 , the polymorph being characterizable as having an X-ray powder diffraction pattern with diffraction lines at °2θ values 4.8, 14.2, 19.1 and 26.8 for Cu Kα radiation of wavelength 1.5406 Angstrom.  
   
   
       20 . A method of preparing a polymorphic form of 9-nitrocamptothecin, the method comprising: 
 crystallizing 9-nitrocamptothecin from acetonitrile.    
   
   
       21 . A method according to  claim 20 , the polymorph being characterizable as having, differential scanning calorimetry, an endotherm at between 273.9 to 275.9° C., and an exotherm at between 279.3 and 281.3° C.  
   
   
       22 . A method according to  claim 20 , the polymorph being characterizable as having an X-ray powder diffraction pattern with diffraction lines at °2θ values 4.8, 14.2, 19.1 and 26.8 for Cu Kα radiation of wavelength 1.5406 Angstrom.