High-strength testosterone undecanoate compositions

Abstract

The present disclosure is drawn to pharmaceutical compositions and oral dosage capsules containing testosterone undecanoate, as well as related methods. The capsule includes a capsule shell and a capsule fill. The capsule fill can include a solubilizer and about 14 wt % to about 35 wt % testosterone undecanoate based on the total capsule fill. The oral dosage capsule is such that when a single oral administration to a male subject of one or more capsules with a total testosterone undecanoate daily dose of about 350 mg to about 650 mg it provides a ratio of serum testosterone C max to serum testosterone C ave of about 2.7 or less. In yet another embodiment, a method for providing a serum concentration of testosterone within a target serum testosterone concentration C ave range for a male subject is provided.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising from about 14 weight % (wt %) to about 35 wt % testosterone undecanoate and a pharmaceutically acceptable carrier, said testosterone undecanoate being not fully dissolved at room temperature. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein at least 5% of said testosterone undecanoate is not dissolved and at least 35% is dissolved, wherein the amount of not dissolved and dissolved testosterone undecanoate is based on the individual solubility of testosterone undecanoate in said pharmaceutical carrier components. 
     
     
         3 . The pharmaceutical composition of  claim 1 , said pharmaceutically acceptable carrier comprising a solubilizer and a dispersant. 
     
     
         4 . The pharmaceutical composition of  claim 1 , comprising a C8-C22 monoglyceride, C8-C22 diglyceride or both. 
     
     
         5 . The pharmaceutical composition of  claim 1 , disposed in a capsule. 
     
     
         6 . The pharmaceutical composition of  claim 1 , said pharmaceutically acceptable carrier comprising a polyoxyethylene hydrogenated vegetable oil, polyethylene glycol or both. 
     
     
         7 . The pharmaceutical composition of  claim 1 , comprising about 50 mg to about 140 mg testosterone undecanoate. 
     
     
         8 . The pharmaceutical composition of  claim 1 , comprising about 75 mg to about 125 mg testosterone undecanoate. 
     
     
         9 . The pharmaceutical composition of  claim 1 , comprising about 14 wt % to about 18 wt % testosterone undecanoate. 
     
     
         10 . A pharmaceutical composition comprising about 75 mg to 125 mg testosterone undecanoate and a pharmaceutically acceptable carrier, said composition having at least 5% of said testosterone undecanoate not dissolved and at least 35% dissolved wherein the amount of not dissolved and dissolved testosterone undecanoate is based on the individual solubility of testosterone undecanoate in said pharmaceutical carrier components. 
     
     
         11 . The pharmaceutical composition of  claim 10 , disposed in a capsule. 
     
     
         12 . The pharmaceutical composition of  claim 10 , comprising a solubilizer, a dispersant, or a solidifying agent. 
     
     
         13 . The pharmaceutical composition of  claim 10 , comprising a C8-C22 monoglyceride, C8-C22 diglyceride or both. 
     
     
         14 . The pharmaceutical composition of  claim 10 , comprising a solubilizer in an amount ranging from 50-86 wt %, a dispersant, and a solidifying agent in an amount ranging from 0.1-25 wt %. 
     
     
         15 . The pharmaceutical composition of  claim 10 , comprising a polyoxyethylene hydrogenated vegetable oil, polyethylene glycol or both. 
     
     
         16 . A pharmaceutical composition comprising about 75 mg to 125 mg testosterone undecanoate and a pharmaceutically acceptable carrier said composition having at least 5% of said testosterone undecanoate not dissolved and at least 35% dissolved wherein the amount of not dissolved and dissolved testosterone undecanoate is based on the individual solubility of testosterone undecanoate in said pharmaceutical carrier components and said pharmaceutically acceptable carrier having a solubilizer in an amount ranging from 50-86 wt %, a dispersant, a solidifying agent in an amount ranging from 0.1-25 wt % or a combination thereof. 
     
     
         17 . The pharmaceutical composition of  claim 16 , disposed in a capsule. 
     
     
         18 . The pharmaceutical composition of  claim 16 , having a solubilizer in an amount ranging from 55-82 wt %, a dispersant, a solidifying agent in an amount ranging from 2-20 wt % or a combination thereof. 
     
     
         19 . The pharmaceutical composition of  claim 16 , comprising a polyoxyethylene hydrogenated vegetable oil, polyethylene glycol or both. 
     
     
         20 . The pharmaceutical composition of  claim 16 , comprising C8-C22 a monoglyceride, C8-C22 diglyceride or both. 
     
     
         21 . The pharmaceutical composition of  claim 16 , comprising a polyoxyethylene hydrogenated vegetable oil, polyethylene glycol, a C8-C22 monoglyceride and a C8-C22 diglyceride. 
     
     
         22 . A pharmaceutical composition comprising 25% to 35% wt % testosterone undecanoate and a pharmaceutically acceptable carrier comprising a solubilizer which is present in the composition in an amount ranging from 50-86 wt %. 
     
     
         23 . The pharmaceutical composition of  claim 22 , further comprising a polyoxyethylene hydrogenated vegetable oil and a C8-C22 diglyceride. 
     
     
         24 . The pharmaceutical composition of  claim 22 , having from about 150 mg to about 250 mg testosterone undecanoate. 
     
     
         25 . The pharmaceutical composition of  claim 22 , further comprising a C8-C22 fatty acid. 
     
     
         26 . The pharmaceutical composition of  claim 25 , said C8-C22 fatty acid selected from the group consisting of capric acid, caprylic acid, undecanoic acid, lauric acid, myristic acid, palmitic acid, stearic, acid, oleic acid, linoleic acid, linolenic acid or a mixture thereof.