Micronized tanaproget and compositions containing same

Abstract

The present invention provides compositions, desirably pharmaceutical compositions, containing micronized tanaproget. The compositions can also contain microcrystalline cellulose, croscarmellose sodium, anhydrous lactose, and magnesium stearate; or can contain microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, povidone, and magnesium stearate. 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 therefore Additional uses include stimulation of food intake.

1 . A pharmaceutical composition comprising micronized tanaproget, or a pharmaceutically acceptable salt thereof, microcrystalline cellulose, croscarmellose sodium, anhydrous lactose, and magnesium stearate.  
   
   
       2 . The composition according to  claim 1 , wherein said tanaproget comprises about 0.08% to about 0.4% wt/wt of said composition.  
   
   
       3 . The composition according to  claim 1 , wherein said tanaproget comprises about 0.35% wt/wt of said composition.  
   
   
       4 . The composition according to  claim 1 , wherein said tanaproget comprises about 0.0875% wt/wt of said composition.  
   
   
       5 . The composition according to  claim 1 , wherein said microcrystalline cellulose comprises about 56% wt/wt of said composition.  
   
   
       6 . The composition according to  claim 1 , wherein said anhydrous lactose comprises about 37% wt/wt of said composition.  
   
   
       7 . The composition according to  claim 1 , wherein said croscarmellose sodium comprises about 6% wt/wt of said composition.  
   
   
       8 . The composition according to  claim 1 , wherein said magnesium stearate comprises about 0.25% wt/wt of said composition.  
   
   
       9 . A pharmaceutical composition comprising micronized tanaproget, or a pharmaceutically acceptable salt thereof, microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, povidone, and magnesium stearate.  
   
   
       10 . The composition according to  claim 9 , wherein said microcrystalline cellulose comprises about 90% wt/wt of said composition.  
   
   
       11 . The composition according to  claim 9 , wherein said croscarmellose sodium comprises about 6% wt/wt of said composition.  
   
   
       12 . The composition according to  claim 9 , wherein said sodium lauryl sulfate comprises about 2% wt/wt of said composition.  
   
   
       13 . The composition according to  claim 9 , wherein said povidone comprises about 1.5% wt/wt of said composition.  
   
   
       14 . The composition according to  claim 9 , wherein said magnesium stearate comprises about 0.25% wt/wt of said composition.  
   
   
       15 . The composition according to  claim 9 , wherein said tanaproget comprises about 0.10% wt/wt of said composition.  
   
   
       16 . A pharmaceutical composition for oral administration comprising about 0.0875% wt/wt micronized tanaproget, about 56.31% wt/wt microcrystalline cellulose, about 6% wt/wt croscarmellose sodium, about 37.35% wt/wt anhydrous lactose, and about 0.25% wt/wt magnesium stearate.  
   
   
       17 . A pharmaceutical composition for oral administration comprising about 0.35% wt/wt micronized tanaproget, about 56.23% wt/wt microcrystalline cellulose, about 6% wt/wt croscarmellose sodium, about 37.17% wt/wt anhydrous lactose, and about 0.25% wt/wt magnesium stearate.  
   
   
       18 . A pharmaceutical composition for oral administration comprising about 0.10% wt/wt micronized tanaproget, about 90.15% wt/wt microcrystalline cellulose, about 6% wt/wt/croscarmellose sodium, about 2% wt/wt sodium lauryl sulfate, about 1.5% wt/wt povidone, and about 0.25% wt/wt magnesium stearate.  
   
   
       19 . The composition according to  claim 1  which degrades less than about 4% over a period of greater than I month at temperatures at or greater than about 25° C. and a relative humidity at or greater than about 60%.  
   
   
       20 . The composition according to  claim 1 , wherein the particles of said micronized tanaproget are less than about 10 μm.  
   
   
       21 . The composition according to  claim 1 , wherein the particles of said composition are less than about 125 μm.  
   
   
       22 . A process for preparing a composition comprising micronized tanaproget, or a pharmaceutically acceptable salt thereof, comprising the steps of: 
 (a) combining said micronized tanaproget, or a pharmaceutically acceptable salt thereof, microcrystalline cellulose, croscarmellose sodium, anhydrous lactose, and magnesium stearate; and    (b) granulating the mixture of step (a).    
   
   
       23 . The process according to  claim 22 , wherein said croscarmellose sodium is intragranular.  
   
   
       24 . The process according to  claim 22 , wherein said croscarmellose sodium is extragranular.  
   
   
       25 . The process according to  claim 22 , wherein said magnesium stearate is intragranular.  
   
   
       26 . The process according to  claim 22 , wherein said composition is compacted and compressed into a tablet suitable for oral administration.  
   
   
       27 . The process according to  claim 26 , wherein said tablet is encapsulated in a capsule.  
   
   
       28 . The process according to  claim 22 , further comprising compacting said composition, milling the composition, or a combination thereof.  
   
   
       29 . The process according to  claim 22 , wherein about 86% to about 99% of said tanaproget is released from said composition after about 90 minutes.  
   
   
       30 . A process for preparing a composition comprising micronized tanaproget, or a pharmaceutically acceptable salt thereof, comprising: 
 (a) combining said tanaproget, microcrystalline cellulose, croscarmellose sodium, povidone, sodium lauryl sulfate, and magnesium stearate; and    (b) granulating the product of step (a).    
   
   
       31 . The process according to  claim 30 , further comprising adding said composition to a capsule.  
   
   
       32 . The process according to  claim 31 , wherein said capsule is a hard shell gelatin capsule.  
   
   
       33 . A capsule comprising the composition of  claim 1 .  
   
   
       34 . A pharmaceutical kit comprising a daily dosage unit of said capsule of  claim 33.