17-hydroxyprogesterone ester-containing oral compositions and related methods

Abstract

The present invention provides for bioavailable oral dosage forms containing esters of 17-hydroxyprogesterone as well as related methods. The oral dosage forms can be formulated for pregnancy support and can include a therapeutically effective amount of an ester of 17-hydroxyprogesterone and a pharmaceutically acceptable carrier. In another embodiment, a pharmaceutically acceptable oral dosage form for pregnancy support is provided. The pharmaceutically acceptable oral dosage can include a therapeutically effective amount of an ester of 17-hydroxyprogesterone and a pharmaceutically acceptable carrier. The oral dosage form can, when measured using a USP Type-II dissolution apparatus in 900 mL of deionized water with 0.5 (w/v) of sodium lauryl sulfate at 50 RPM at 37° C., release at least 20 wt % of the dose of the ester of 17-hydroxyprogesterone after 60 minutes, or in the alternative release at least 20 wt % more after 60 minutes than an equivalently dosed oral dosage form without the carrier.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising a therapeutically effective amount of 17-hydroxyprogesterone caproate and a pharmaceutically acceptable carrier comprising a lipophilic additive selected from benzyl benzoate, castor oil and mixtures thereof, said lipophilic additive comprising at least 50 weight/weight percent (w/w %) of the carrier and said pharmaceutical composition having 50 w/w % or less castor oil and 50 w/w % or less benzyl benzoate wherein said pharmaceutical composition when measured using a USP Type-II dissolution apparatus in 900 mL of simulated intestinal fluid having 0.5 w/w % sodium lauryl sulfate at 50 RPM at 37° C., releases at least 20% of the 17-hydroxyprogesterone caproate at 60 minutes with the proviso that the composition does not include benzyl alcohol. 
     
     
         2 . The pharmaceutical composition of  claim 1 , in a capsule. 
     
     
         3 . The pharmaceutical composition of  claim 1 , formulated as a tablet. 
     
     
         4 . The pharmaceutical composition of  claim 2 , wherein capsule includes from about 30 mg to about 300 mg of 17-hydroxyprogesterone caproate. 
     
     
         5 . The pharmaceutical composition of  claim 3 , wherein the tablet includes from about 20 mg to about 800 mg of 17-hydroxyprogesterone caproate. 
     
     
         6 . The pharmaceutical composition of  claim 1 , which is a controlled release dosage form. The pharmaceutical composition of  claim 2 , wherein the ratio of the amount of 17-hydroxyprogesterone caproate in the composition to the fill volume of the capsule is from about 0.02 g/mL to about 0.8 g/mL. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the carrier includes a hydrophilic additive. 
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein the carrier includes a lipophilic additive. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the carrier includes at least one hydrophilic additive and at least one lipophilic additive at a lipophilic additive to hydrophilic additive ratio of about 90:10 to about 1:99. 
     
     
         11 . The pharmaceutical composition of  claim 1 , having from about 28 to about 48 w/w % benzyl benzoate. 
     
     
         12 . The pharmaceutical composition of  claim 1 , having about 23 to about 25 w/w % castor oil. 
     
     
         13 . The pharmaceutical composition of  claim 1 , having about 5 to about 30 w/w 17-hydroxyprogesterone caproate. 
     
     
         14 . The pharmaceutical composition of  claim 1 , having about 25% w/w % 17-hydroxyprogesterone caproate. 
     
     
         15 . The pharmaceutical composition of  claim 1 , wherein the 17-hydroxyprogesterone caproate is fully solubilized. 
     
     
         16 . A pharmaceutical composition comprising a therapeutically effective amount of 17-hydroxyprogesterone caproate and a pharmaceutically acceptable carrier comprising a lipophilic additive selected from benzyl benzoate, castor oil and mixtures thereof, said lipophilic additive comprising at least 50 weight/weight percent (w/w %) of the carrier and said pharmaceutical composition having 50 w/w % or less castor oil and 50 w/w % or less benzyl benzoate wherein said pharmaceutical composition is prepared by combining castor oil, benzyl benzoate and 17-hydroxyprogesterone caproate with the provisio that benzyl alcohol is not combined with the pharmaceutical composition. 
     
     
         17 . A method of treating a pregnant female at risk of having a preterm birth, said method comprising administration to said pregnant female the pharmaceutical composition of  claim 1 .