Tanaproget compositions containing ethinyl estradiol

Abstract

Compositions containing micronized tanaproget, or a pharmaceutically acceptable salt thereof, and ethinyl estradiol and methods of preparing the same are provided. Also provided are kits containing the compositions, methods of contraception and hormone replacement therapy including administering a composition containing micronized tanaproget and ethinyl estradiol.

1 . A pharmaceutical composition comprising an effective amount of micronized tanaproget, or a pharmaceutically acceptable salt thereof, and an effective amount of ethinyl estradiol.  
     
     
         2 . The composition according to  claim 1 , wherein said tanaproget comprises about 0.1% to about 1% wt/wt of said composition.  
     
     
         3 . The composition according to  claim 2 , wherein said tanaproget comprises about 0.17% to about 0.53% wt/wt of said composition.  
     
     
         4 . The composition according to  claim 2 , wherein said tanaproget comprises about 0.17% wt/wt of said composition.  
     
     
         5 . The composition according to  claim 2 , wherein said tanaproget comprises about 0.35% wt/wt of said composition.  
     
     
         6 . The composition according to  claim 2 , wherein said tanaproget comprises about 0.52% wt/wt of said composition.  
     
     
         7 . The composition according to  claim 1 , wherein said ethinyl estradiol comprises about 0.03 to about 0.05% wt/wt of said composition.  
     
     
         8 . The composition according to  claim 7 , wherein said ethinyl estradiol comprises about 0.035% wt/wt of said composition.  
     
     
         9 . The composition according to  claim 1 , wherein said ethinyl estradiol is a 2% triturate in lactose.  
     
     
         10 . The composition according to  claim 9 , wherein said ethinyl estradiol 2% triturate in lactose comprises about 1.75% of said composition.  
     
     
         11 . The composition according to  claim 1 , further comprising microcrystalline cellulose, anhydrous lactose, croscarmellose sodium, and magnesium stearate  
     
     
         12 . The composition according to  claim 11 , wherein said microcrystalline cellulose comprises about 30 to about 56% wt/wt of said composition.  
     
     
         13 . The composition according to  claim 11 , wherein said anhydrous lactose comprises about 30 to about 56% wt/wt of said composition  
     
     
         14 . The composition according to  claim 11 , wherein said croscarmellose sodium comprises about 2 to about 6% wt/wt of said composition.  
     
     
         15 . The composition according to  claim 11 , wherein said magnesium stearate comprises about 0.25 to about 0.5% wt/wt of said composition.  
     
     
         16 . The composition according to  claim 11 , comprising about 0.175% wt/wt of micronized tanaproget, or a pharmaceutically acceptable salt thereof, about 0.035% wt/wt of ethinyl estradiol, about 54.5% wt/wt of microcrystalline cellulose, about 37.3% wt/wt of anhydrous lactose, about 6% wt/wt of croscarmellose sodium, and about 0.25% wt/wt of magnesium stearate.  
     
     
         17 . The composition according to  claim 1 , comprising about 0.35% wt/wt of micronized tanaproget, or a pharmaceutically acceptable salt thereof, about 0.035% wt/wt of ethinyl estradiol, about 54.4% wt/wt of microcrystalline cellulose, about 37.2% wt/wt of anhydrous lactose, about 6% wt/wt of croscarmellose sodium, and about 0.25% wt/wt of magnesium stearate.  
     
     
         18 . The composition according to  claim 11 , comprising about 0.525% wt/wt of micronized tanaproget, or a pharmaceutically acceptable salt thereof, about 0.035% wt/wt of ethinyl estradiol, about 54.3% wt/wt of microcrystalline cellulose, about 37.1% wt/wt/ of anhydrous lactose, about 6% wt/wt of croscarmellose sodium, and about 0.25% wt/wt of magnesium stearate.  
     
     
         19 . A process for preparing an oral composition comprising micronized tanaproget, or a pharmaceutically acceptable salt thereof, comprising: 
 (a) mixing said micronized tanaproget, or a pharmaceutically acceptable salt thereof, and ethinyl estradiol; and    (b) granulating the product of step (a).    
     
     
         20 . The process according to  claim 19 , wherein step (a) further comprises microcrystalline cellulose, croscarmellose sodium, anhydrous lactose, and magnesium stearate.  
     
     
         21 . The process according to  claim 19 , wherein said composition is compacted and compressed into a tablet suitable for oral administration.  
     
     
         22 . The process according to  claim 21 , wherein said tablet is encapsulated in a capsule.  
     
     
         23 . A pharmaceutical kit comprising a daily dosage unit of said tablet of  claim 21 .  
     
     
         24 . A pharmaceutical kit comprising a daily dosage unit of said capsule of  claim 22 .  
     
     
         25 . A pharmaceutically useful kit which comprises: 
 (a) a first phase of 14 to 21 daily dosage units of a formulation comprising tanaproget and ethinyl estradiol; and    (b) a second phase of 0 to 7 daily dosage units of an orally and pharmaceutically acceptable placebo;    wherein the total number of the daily dosage units is 28.    
     
     
         26 . The kit according to  claim 25 , further comprising an antiprogestin.  
     
     
         27 . The kit according to  claim 25 , wherein said formulation comprises about 100 μg, 200 μg, or 300 μg of tanaproget.  
     
     
         28 . The kit according to  claim 25 , wherein said formulation comprises about 20 μg of ethinyl estradiol.  
     
     
         29 . A method of contraception comprising administering to a female of child bearing age a composition of  claim 1 .  
     
     
         30 . A method of hormone replacement therapy comprising administering to a female in need thereof a composition of  claim 1.