Hdac inhibitor solid state forms

Abstract

The present disclosure relates to the crystalline mesylate Form 1 salt of N-hydroxy 2-{6-[(6-fluoro-quinolin-2-ylmethyl)-amino]-3-aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide and methods of making the same. The crystalline mesylate Form 1 salt of N-hydroxy 2-{(6-[(6-fluoro-quinolin-2-ylmethyl)-amino]-3-aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide is useful in preparation of pharmaceutical compositions and dosage forms for the treatment of cancer, immune disorders and inflammation.

1 - 20 . (canceled) 
     
     
         21 . A pharmaceutical composition comprising Crystalline mesylate Form 1 salt of N-hydroxy 2-{6-[(6-fluoro-quinolin-2-ylmethyl)-amino]-3 -aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carb oxamide and one or more pharmaceutically acceptable excipients or carriers. 
     
     
         22 . The pharmaceutical composition of  claim 21 , wherein the crystalline mesylate is characterized by an X-ray diffraction pattern reflection at a 2 theta value of 3.7°±0.3. 
     
     
         23 . The pharmaceutical composition of  claim 22 , wherein the crystalline mesylate is further characterized by an X-ray diffraction pattern reflection at a 2 theta value of 14.9°±0.3. 
     
     
         24 . The pharmaceutical composition of  claim 22 , wherein the crystalline mesylate is further characterized by an X-ray diffraction pattern reflection at a 2 theta value of 7.5°±0.3. (NEW) The pharmaceutical composition of  claim 23 , wherein the crystalline mesylate is further characterized by an X-ray diffraction pattern reflection at a 2 theta value of 7.5°±0.3. 
     
     
         26 . The pharmaceutical composition of  claim 22 , wherein the crystalline mesylate is further characterized by at least one X-ray diffraction pattern reflection selected from a 2 theta value of 7.5°±0.3, 14.9°±0.3, 17.3°±0.3, 19.7°±0.3, 22.5°±0.3, 22.9°±0.3, or 
     
     
         27 . The pharmaceutical composition of  claim 22 , wherein the crystalline mesylate is further characterized by at least two X-ray diffraction pattern reflections selected from a 2 theta value of 7.5°±0.3, 14.9°±0.3, 17.3°±0.3, 19.7°±0.3, 22.5°±0.3, 22.9°±0.3, or 
     
     
         28 . The pharmaceutical composition of  claim 22 , wherein the crystalline mesylate is further characterized by at least three X-ray diffraction pattern reflections selected from a 2 theta value of 7.5°±0.3, 14.9°±0.3, 17.3 °±0.3, 19.7°±0.3, 22.5°±0.3, 22.9°±0.3, or 
     
     
         29 . The pharmaceutical composition of  claim 22 , wherein the crystalline mesylate is further characterized by at least four X-ray diffraction pattern reflections selected from a 2 theta value of 7.5°±0.3, 14.9°±0.3, 17.3°±0.3, 19.7°±0.3, 22.5°±0.3, 22.9°±0.3, or 
     
     
         30 . The pharmaceutical composition of  claim 22 , wherein the crystalline mesylate is further characterized by at least five X-ray diffraction pattern reflections selected from a 2 theta value of 7.5°±0.3, 14.9°±0.3, 17.3°±0.3, 19.7°±0.3, 22.5°±0.3, 22.9°±0.3, or 
     
     
         31 . The pharmaceutical composition of  claim 22 , wherein the crystalline mesylate is characterized by the X-ray powder diffraction pattern as shown in  FIG.  1   . 
     
     
         32 . The pharmaceutical composition of  claim 22 , wherein the crystalline mesylate is characterized by thermogravimetric analysis (TGA), wherein the TGA thermogram exhibits less than 0.5%±0.5 weight loss up to 225° C.±10.0. 
     
     
         33 . The pharmaceutical composition of  claim 22 , wherein the crystalline mesylate is characterized by the thermogravimetric analysis (TGA) pattern as shown in  FIG.  3   . 
     
     
         34 . The pharmaceutical composition of  claim 22 , wherein the crystalline mesylate is characterized by characterized by differential scanning calorimetry (DSC), wherein the DSC thermogram exhibits a single exothermic event with an onset temperature at about 222.1° C±5.0 (433 J/g) or an exothermic peak at 225.8° C.±5.0. (NEW) The pharmaceutical composition of  claim 22 , wherein the crystalline mesylate is characterized by the differential scanning calorimetry (DSC) pattern as shown in  FIG.  3   . 
     
     
         36 . The pharmaceutical composition of  claim 22 , wherein an amount of another crystalline form or an amorphous form in the crystalline mesylate is 5% (w/w) or less. 
     
     
         37 . The pharmaceutical composition of  claim 22 , wherein the amount of impurities in the crystalline mesylate is 3% or less. 
     
     
         38 . The pharmaceutical composition of  claim 22 , further comprising one or more additional active pharmaceutical ingredient (API). 
     
     
         39 . The pharmaceutical composition of  claim 38 , wherein the additional API is valganciclovir. 
     
     
         40 . A method of treating cancer in an individual, the method comprising administering an effective amount of:
 (a) valganciclovir; and   (b) Crystalline mesylate Form 1 salt of N-hydroxy 2-{6-[(6-fluoro-quinolin-2-ylmethyl)-amino]-3-aza-bicydo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide characterized by an X-ray diffraction pattern reflection at a 2 theta value of 3.7°±0.3   thereby treating the cancer in the individual.