Micronized tanaproget, compositions, and methods of preparing the same

Abstract

The present invention provides compositions, desirably pharmaceutical compositions, containing micronized tanaproget. The compositions can also contain microcrystalline cellulose, croscarmellose sodium, anhydrous lactose, magnesium stearate, micronized edetate calcium disodium hydrous, and micronized sodium thiosulfate pentahydrate. The compositions are useful in contraception and hormone replacement therapy and in the treatment and/or prevention of uterine myometrial fibroids, benign prostatic hypertrophy, benign and malignant neoplastic disease, dysfunctional bleeding, uterine leiomyomata, endometriosis, polycystic ovary syndrome, and carcinomas and adenocarcinomas of the pituitary, endometrium, kidney, ovary, breast, colon, and prostate and other hormone-dependent tumors, and in the preparation of medicaments useful therefor. Additional uses include stimulation of food intake.

What is claimed is: 
     
         1 . A method of contraception, hormone replacement therapy, stimulating food intake, or treating or preventing (i) endometriosis, (ii) uterine myometrial fibroids, (iii) benign prostatic hypertrophy, (iv) benign and malignant neoplastic disease, (v) dysfunctional bleeding, (vi) uterine leiomyomata, (vii) polycystic ovary syndrome or (viii) carcinomas and adenocarcinomas of the pituitary, endometrium, kidney, ovary, breast, colon, prostate, or other hormone dependent tumors in a patient in need thereof, said method comprising administering a composition comprising an intragranulation comprising micronized tanaproget or a pharmaceutically acceptable salt thereof, microcrystalline cellulose, croscarmellose sodium, anhydrous lactose, magnesium stearate, micronized edetate calcium disodium hydrous, and micronized sodium thiosulfate pentahydrate to said patient. 
     
     
         2 . The method according to  claim 1 , wherein the particles of said micronized tanaproget are less than about 10 μm. 
     
     
         3 . The method according to  claim 1 , wherein the particles of said micronized sodium thiosulfate pentahydrate are less than about 31 μm. 
     
     
         4 . The method according to  claim 1 , wherein the particles of said micronized edetate calcium disodium hydrous are less than about 35 μm. 
     
     
         5 . The method according to  claim 1 , which degrades less than about 3% over a period of greater than 1 month at temperatures at or greater than about 25° C. and a relative humidity at or greater than about 60%. 
     
     
         6 . The method according to  claim 1 , wherein said tanaproget comprises about 0.15% to about 0.50% wt/wt of said composition. 
     
     
         7 . The method according to  claim 1 , wherein said tanaproget comprises about 0.15% wt/wt of said composition. 
     
     
         8 . The method according to  claim 1 , wherein said tanaproget comprises about 0.23% wt/wt of said composition. 
     
     
         9 . The method according to  claim 1 , wherein said tanaproget comprises about 0.31% wt/wt of said composition. 
     
     
         10 . The method according to  claim 1 , wherein said tanaproget comprises about 0.5% wt/wt of said composition. 
     
     
         11 . The method according to  claim 1 , wherein said microcrystalline cellulose comprises about 30 to about 50% wt/wt of said composition. 
     
     
         12 . The method according to  claim 1 , said composition further comprising extragranular croscarmellose sodium. 
     
     
         13 . The method according to  claim 12 , wherein said intragranular and extragranular croscarmellose sodium comprises about 2 to about 6% wt/wt of said composition. 
     
     
         14 . The method according to  claim 1 , said composition further comprising extragranular magnesium stearate. 
     
     
         15 . The method according to  claim 1 , wherein said intragranular and extragranular magnesium stearate comprises about 0.25 to about 0.5% wt/wt of said composition. 
     
     
         16 . The method according to  claim 1 , wherein said anhydrous lactose comprises about 54% to about 55% wt/wt of said composition. 
     
     
         17 . The method according to  claim 1 , wherein said micronized edetate calcium disodium hydrous comprises about 0.05 to about 0.15% wt/wt of said composition. 
     
     
         18 . The method according to  claim 1 , wherein said micronized sodium thiosulfate pentahydrate comprises about 0.25 to about 0.75% wt/wt of said composition. 
     
     
         19 . The method according to  claim 1 , wherein the particles of said composition are less than about 100 μm. 
     
     
         20 . The method according to  claim 1 , wherein said composition is administered to said female as a tablet.