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.

1 . An oral pharmaceutical composition comprising:
 a therapeutically effective amount of 17-hydroxyprogesterone caproate, and a pharmaceutically acceptable carrier said therapeutically effective amount ranging from 150 mg to 750 mg 17-hydroxyprogesterone caproate.   
     
     
         2 . The oral pharmaceutical pharmaceutical composition of  claim 1 , wherein the composition releases greater than 10% after 1 hour when tested using a USP Type II apparatus at 50 rpm in an aqueous media having 1.5× or greater sink condition at 37.0° C. (±0.5). 
     
     
         3 . The oral pharmaceutical pharmaceutical composition of  claim 1 , wherein the composition releases greater than 10% after 1 hour when tested using a USP Type II apparatus at 50 rpm in an aqueous media having 3× or greater sink condition at 37.0° C. (±0.5). 
     
     
         4 . The oral pharmaceutical composition of  claim 1 , wherein the composition has from about 225 mg to 800 mg of 17-hydroxyprogesterone caproate. 
     
     
         5 . The oral pharmaceutical composition of  claim 1 , said pharmaceutically acceptable carrier having one or more of a diluent, binder, disintegrant, lubricant or surfactant. 
     
     
         6 . The oral pharmaceutical composition of  claim 1 , said pharmaceutically acceptable carrier having a lipophilic or hydrophilic additive. 
     
     
         7 . The oral pharmaceutical composition of  claim 1 , said pharmaceutically acceptable carrier having a lipophilic or hydrophilic surfactant. 
     
     
         8 . The oral pharmaceutical composition of  claim 1 , said pharmaceutically acceptable carrier having a lipophilic or hydrophilic surfactant. 
     
     
         9 . The oral pharmaceutical composition of  claim 1 , said pharmaceutically acceptable carrier having a non-ionic or ionic surfactant. 
     
     
         10 . The oral pharmaceutical composition of  claim 1 , said 17HPC being fully solubilized, partially solubilized, crystalline particulate, amorphous particulate, or a combination thereof 
     
     
         11 . The oral pharmaceutical composition of  claim 1 , said 17HPC being particulate and having a mean particle diameter of less than 200 nm, from 200 to 500 nm, from 500 to 1000 nm, from 1 to 50 μm, from 50 to 250 μm, from 250 to 500 μm, from 500 to 1000 μm, or greater than 1000 μm. 
     
     
         12 . The oral pharmaceutical composition of  claim 1 , said 17HPC being particulate and having a mean particle diameter of from 50-40 μm, 40-30 μm, 30-20 μm, 20-10 μm , or 10-1 μm. 
     
     
         13 . The oral pharmaceutical composition of  claim 1 , wherein the composition has a crystallization inhibitor or a particle agglomeration inhibitor. 
     
     
         14 . The oral pharmaceutical composition of  claim 1 , wherein the composition is a powder, granulate, particulate, bead, pellet, sprinkle, suspension, solution, tablet, caplet, capsule, or a combination thereof 
     
     
         15 . The oral pharmaceutical composition of  claim 1 , wherein the composition is controlled release or immediate release. 
     
     
         16 . The oral pharmaceutical composition of  claim 1 , wherein the compmosition is a coated or uncoated tablet or caplet. 
     
     
         17 . The oral pharmaceutical composition of  claim 1 , wherein the composition is a monolithic or multilayered tablet. 
     
     
         18 . The oral pharmaceutical composition of  claim 1 , which when administered once, twice or three times a day as one to twelve unit dosage forms total per day to human subject, provides a 17-hydroxyprogesterone caproate C avg-24h  of greater than about 0.1, 0.5 or 1.0 ng/mL. 
     
     
         19 . A method of treatment said method comprising administering to a subject an oral pharmaceutical composition comprising:
 a therapeutically effective amount of 17-hydroxyprogesterone caproate, and a pharmaceutically acceptable carrier and one or more additional agents chosen from pharmaceutical agents, vitamins, minerals, supplements.   
     
     
         20 . The method of  claim 19 , wherein said method comprises administering said pharmaceutical composition once, twice or three times a day as one to twelve unit dosage forms total per day to human subject, to provide a 17-hydroxyprogesterone caproate C avg-24h  of greater than about 0.1, 0.5 or 1.0 ng/mL. 
     
     
         21 - 61 . (canceled)