Novel crystalline forms of temozolomide

Abstract

Disclosed are novel crystalline forms of Temozolomide, methods of preparation thereof, medicaments including the novel crystalline forms of Temozolomide, and uses thereof in the treatment of medical conditions.

1 . Crystalline Temozolomide Form VIII comprising at least one characteristic selected from a powder X-ray diffraction pattern exhibiting peaks at diffraction angles 2θ of about 9.3, 10.8, 11.8, 14.7, 19.7, 26.6, 28.2 and 28.8±0.2°; and an infrared spectrum with υ max  at about 1678, 731 and 712±4 cm −1 . 
   
   
       2 . The Temozolomide Form VIII of  claim 1 , wherein the powder X-ray diffraction pattern is substantially as depicted in  FIG. 17 . 
   
   
       3 . The Temozolomide Form VIII of  claim 1 , wherein the infrared spectrum is substantially as depicted in  FIG. 18 . 
   
   
       4 . A process of preparing crystalline Temozolomide Form VIII of  claim 1 , the process comprising:
 contacting Temozolomide with a solvent comprising acetone, dichloromethane, or a combination thereof, to form a Temozolomide solution;   crystallizing Temozolomide from the solution, to thereby obtain crystalline Temozolomide Form VIII; and   isolating the crystalline Temozolomide Form VIII,   
     wherein when the solvent includes acetone, the acetone contains less than 5% by weight water. 
   
   
       5 . A pharmaceutical composition comprising Temozolomide Form VIII of  claim 1  and a pharmaceutically acceptable carrier. 
   
   
       6 . A method of therapeutically or prophylactically treating a cancer, the method comprising administering to a mammal in need thereof a therapeutically effective amount of Temozolomide Form VIII of  claim 1 . 
   
   
       7 . The method of  claim 6 , wherein the cancer is brain cancer, breast cancer, refractory anaplastic astrocytoma, malignant glioma, glioblastoma multiforme or anaplastic astrocytoma. 
   
   
       8 . The method of  claim 6 , wherein the mammal is human. 
   
   
       9 . The method of  claim 6 , wherein the temozolomide is administered in one or more dosages of from about 1 mg to about 250 mg per dose. 
   
   
       10 . The method of  claim 9 , wherein one or more of the dosages is about 5 mg, about 20 mg, about 100 mg, or about 250 mg per dose.