Crystalline forms of deuterium-enriched pioglitazone

Abstract

Provided herein are crystalline forms of deuterium-enriched (R)-pioglitazone and compositions thereof. Also provided herein are methods of using the crystalline forms of deuterium-enriched (R)-pioglitazone and compositions thereof.

1 . A deuterium chloride salt of a deuterium-enriched compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein R 1  is H or D, provided that the total deuterium abundance in the compound of formula (I) is about 1.3 to about 4. 
       
     
     
         2 . The deuterium chloride salt of  claim 1 , wherein the deuterium chloride salt is a crystalline deuterium chloride salt. 
     
     
         3 . The deuterium chloride salt of  claim 1 , wherein the crystalline deuterium chloride salt is an anhydrous crystalline deuterium chloride salt. 
     
     
         4 . A crystalline deuterium chloride salt of a deuterium-enriched compound of formula (I) 
       
         
           
           
               
               
           
         
         wherein R 1  is H or D, provided that the total deuterium abundance in the compound of formula (I) is about 1.3 to about 4, and 
         wherein the crystalline deuterium chloride salt is characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 15.8°±0.2°, 22.8°±0.2°, and 26.0°±0.2°. 
       
     
     
         5 . The crystalline deuterium chloride salt of  claim 4 , wherein the crystalline deuterium chloride salt is characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 8.6°±0.2°, 8.8°±0.2°, 12.8°±0.2°, 12.9°±0.2°, 15.8°±0.2°, 18.8°±0.2°, 18.9°±0.2°, 19.7°±0.2°, 20.0°±0.2°, 20.8°±0.2°, 22.8°±0.2°, 26.0°±0.2°, and 31.3°±0.2°. 
     
     
         6 . The crystalline deuterium chloride salt of  claim 4 , wherein the crystalline deuterium chloride salt is characterized by an X-ray powder diffraction pattern substantially the same as shown in  FIG.  1 A . 
     
     
         7 . The crystalline deuterium chloride salt of  claim 4 , wherein the crystalline deuterium chloride salt has a melting point onset as determined by differential scanning calorimetry at about 190° C. to about 200° C. 
     
     
         8 . The crystalline deuterium chloride salt of  claim 4 , wherein the crystalline deuterium chloride salt is an anhydrous crystalline deuterium chloride salt. 
     
     
         9 - 29 . (canceled) 
     
     
         30 . A pharmaceutical composition comprising a deuterium chloride salt of  claim 1 , and a pharmaceutically acceptable excipient. 
     
     
         31 . A pharmaceutical composition comprising a crystalline deuterium chloride salt of  claim 4 , and a pharmaceutically acceptable excipient. 
     
     
         32 . A method of treating a metabolic disorder in a patient in need thereof, the method comprising administering to the patient an effective amount of a deuterium chloride salt of  claim 1 . 
     
     
         33 . The method of  claim 32 , wherein the metabolic disorder is polycystic ovary syndrome. 
     
     
         34 . A method of treating diabetes mellitus type 2 in a patient in need thereof, the method comprising administering to the patient an effective amount of a deuterium chloride salt of  claim 1 . 
     
     
         35 . A method of treating nonalcoholic steatohepatitis in a patient in need thereof, the method comprising administering to the patient an effective amount of a deuterium chloride salt of  claim 1 . 
     
     
         36 . A method of treating nonalcoholic fatty liver disease in a patient in need thereof, the method comprising administering to the patient an effective amount of a deuterium chloride salt of  claim 1 . 
     
     
         37 . A method of treating a neurological disorder in a patient in need thereof, the method comprising administering to the patient an effective amount of a deuterium chloride salt of  claim 1 . 
     
     
         38 . The method of  claim 37 , wherein the neurological disorder is adrenoleukodystrophy or adrenomyeloneuropathy. 
     
     
         39 - 45 . (canceled)