Progesterone formulations having a desirable pk profile

Abstract

This disclosure provides progesterone formulations, methods of using these formulations, and their related pharmacokinetic parameters. In particular embodiments, the formulations disclosed herein allow for a reduction in the amount of progesterone administered to a patient in need thereof, while still providing the benefits of a larger dosage amount.

What is claimed is: 
     
         1 . A pharmaceutical composition for orally administering progesterone to a subject in need thereof, the composition comprising:
 an amount of progesterone;   a solubilizing agent; and   a nonionic surfactant selected from the group consisting of lauroyl macrogol-32 glycerides EP (GELUCIRE 44/11), lauroyl polyoxyl-32 glycerides (GELUCIRE 44/14), and caprylocaproyl macrogol-8 glycerides EP;   wherein the solubilizing agent comprises at least one C 6 -C 12  fatty acid mono-, di-, or tri-ester of glycerol and wherein the composition has a total mass.   
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the solubilizing agent comprises at least one C 6 -C 12  fatty acid mono-ester of glycerol. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the solubilizing agent comprises at least one C 6 -C 12  fatty acid di-ester of glycerol. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the solubilizing agent comprises at least one C 6 -C 12  fatty acid tri-ester of glycerol. 
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein the tri-ester of glycerol comprises predominantly esters of caprylic fatty acid (C 8 ) and capric fatty acid (C 10 ). 
     
     
         6 . The pharmaceutical composition of  claim 4 , wherein the tri-ester of glycerol is MIGLYOL® 812. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the solubilizing agent is medium chain triglycerides (MIGLYOL® 812). 
     
     
         8 . The pharmaceutical composition of  claim 7 , wherein the nonionic surfactant is lauroyl polyoxyl-32 glycerides (GELUCIRE® 44/14). 
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein the amount of progesterone is from 25 mg to 200 mg. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the amount of progesterone is 75 mg or 150 mg. 
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein the amount of progesterone includes a solubilized amount of progesterone and a suspended amount of progesterone. 
     
     
         12 . The pharmaceutical composition of  claim 1 , wherein the composition is provided in a gelatin capsule. 
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein the total mass of the composition is less than 500 mg. 
     
     
         14 . The pharmaceutical composition of  claim 1 , wherein the composition provides increased progesterone bioavailability compared to micronized progesterone suspended in peanut oil. 
     
     
         15 . The pharmaceutical composition of claim,  1  wherein the solubilizing agent comprises predominantly at least one C 6 -C 12  fatty acid mono-, di-, or tri-ester of glycerol. 
     
     
         16 . A pharmaceutical composition for orally administering progesterone to a subject in need thereof, the composition comprising:
 75, 150, 200, or 300 mg of progesterone;   a solubilizing agent comprising predominantly a triglyceride oil of C8 and C10 fatty acid esters; and   lauroyl polyoxyl-32 glycerides (GELUCIRE 44/14).   
     
     
         17 . A method of preventing endometrial hyperplasia, the method comprising administering to a patient in need thereof a composition according to  claim 1 . 
     
     
         18 . The method of preventing endometrial hyperplasia of  claim 17 , wherein the amount of progesterone is 150 mg. 
     
     
         19 . A method of treating amenorrhea, the method comprising administering to a patient in need thereof a composition according to  claim 1 . 
     
     
         20 . The method of treating amenorrhea of  claim 19 , wherein the amount of progesterone is 150 mg or 300 mg. 
     
     
         21 . The pharmaceutical composition of  claim 1 , wherein the amount of progesterone comprises about 33% by weight of the composition; the solubilizing agent comprises about 65% by weight of the composition, the non-ionic surfactant comprises about 1.7% by weight of the composition. 
     
     
         22 . The pharmaceutical composition of  claim 1 , wherein the amount of progesterone comprises about 33.33% by weight of the composition; the solubilizing agent comprises about 64.93% by weight of the composition, the non-ionic surfactant comprises about 1.67% by weight of the composition. 
     
     
         23 . The pharmaceutical composition of  claim 21 , further comprising an antioxidant. 
     
     
         24 . The pharmaceutical composition of  claim 23 , wherein the antioxidant is butylated hydroxy toluene. 
     
     
         25 . The pharmaceutical composition of  claim 21 , wherein the solubilizing agent is MIGLYOL 812. 
     
     
         26 . The pharmaceutical composition of  claim 25 , wherein the non-ionic surfactant is lauroyl polyoxyl-32 glycerides (GELUCIRE 44/14). 
     
     
         27 . The pharmaceutical composition of  claim 26 , wherein the amount of progesterone is 200 mg. 
     
     
         28 . The pharmaceutical composition of  claim 26 , wherein the amount of progesterone is 150 mg.