Polymorph Form II of Tanaproget

Abstract

Tanaproget polymorph Form II, processes for preparing tanaproget polymorph Form II, pharmaceutical compositions including tanaproget polymorph Form II, micronized tanaproget polymorph Form II, and processes for converting Form II to tanaproget Form I are provided. Also provided are methods of contraception, hormone replacement therapy, stimulation of food intake and treating or preventing uterine myometrial fibroids, benign prostatic hypertrophy, benign and malignant neoplastic disease, dysfunctional bleeding, uterine leiomyomata, endometriosis, polycystic ovary syndrome, or carcinomas and adenocarcinomas comprising administering polymorph Form II to a mammalian subject.

1 . A process for preparing polymorph Form I of tanaproget, said process comprising heating polymorph Form II of tanaproget. 
     
     
         2 . The process according to  claim 1 , wherein said polymorph Form II of tanaproget is heated to a temperature of about 219 to about 226° C. 
     
     
         3 . The process according to  claim 1 , wherein said polyrmorph Form I of tanparoget recrystallizes from the melted polymorph Form II of tanaproget. 
     
     
         4 . The process according to  claim 1 , wherein said polymorph Form II of tanaproget has:
 (a) an X-ray diffraction peak pattern comprising peaks at 2θ of about 6.0°, 8.3°, 12.0°, 21.4°, and 23.4°; and   (b) a differential scanning calorimetry thermogram having a T onset  of about 219° C.   
     
     
         5 . A process for preparing polymorph Form I of tanaproget, said process comprising combining polymorph Form II of tanaproget with acetone and water. 
     
     
         6 . The process according to  claim 5 , wherein the ratio of acetone to water is 1:1. 
     
     
         7 . The process according to  claim 5 , wherein said polymorph Form II of tanaproget has:
 (a) an X-ray diffraction peak pattern comprising peaks at 2θ of about 6.0°, 8.3°, 12.0°, 21.4°, and 23.4°; and   (b) a differential scanning calorimetry thermogram having a T onset  of about 219° C.   
     
     
         8 . A method of preparing a pharmaceutical composition comprising polymorph Form II of tanaproget, said method comprising combining polymorph Form II of tanaproget and one of more of:
 (i) a metal chelator;   (ii) a pH adjuster;   (iii) a surfactant;   (iv) at least one filler;   (v) a binder;   (vi) a disintegrant; and   (vii) a lubricant.   
     
     
         9 . A method of hormone replacement therapy comprising administering polymorph Form II of tanaproget to a female. 
     
     
         10 . The method according to  claim 9 , wherein said polymorph Form II of tanaproget has:
 (a) an X-ray diffraction peak pattern comprising peaks at 2θ of about 6.0°, 8.3°, 12.0°, 21.4°, and 23.4°; and   (b) a differential scanning calorimetry thermogram having a T onset  of about 219° C.   
     
     
         11 . A method of stimulating food intake or treating or preventing uterine myometrial fibroids, benign prostatic hypertrophy, benign and malignant neoplastic disease, dysfunctional bleeding, uterine leiomyomata, endometriosis, polycystic ovary syndrome, or carcinomas and adenocarcinomas comprising administering polymorph Form II of tanaproget to a mammalian subject. 
     
     
         12 . The method according to  claim 11 , wherein said polymorph Form ll of tanaproget has:
 (a) an X-ray diffraction peak pattern comprising peaks at 2θ of about 6.0°, 8.3°, 12.0°, 21.4°, and 23.4°; and   (b) a differential scanning calorimetry thermogram having a T onset  of about 219° C.