Testosterone undecanoate compositions

Abstract

The present disclosure is drawn to pharmaceutical compositions and oral dosage forms containing testosterone undecanoate, as well as related methods of treatment. In one embodiment, the oral dosage form can include a therapeutically effective amount of testosterone undecanoate and a pharmaceutically acceptable carrier. The dosage form can be formulated such that, when measured using a USP Type II apparatus in 1000 mL of 8 wt % Triton X-100 in water at 37° C. and 100 rpm, the oral dosage form releases at least 20% more testosterone undecanoate after the first 120 minutes than an equivalent dose testosterone undecanoate containing oral dosage form without the pharmaceutically acceptable carrier.

1 . A solid oral dosage form, comprising:
 a therapeutically effective amount of testosterone undecanoate, and   a pharmaceutically acceptable carrier,   wherein when tested using a USP Type II apparatus in 1000 mL of 8 wt % Triton X-100 in water at 37° C. and 100 rpm, the oral dosage form releases at least 20% more testosterone undecanoate after the first 120 minutes than an equivalent dose testosterone undecanoate containing oral dosage form without the pharmaceutically acceptable carrier.   
     
     
         2 . The solid oral dosage form of  claim 1 , wherein the testosterone undecanoate is present as a solid particulate. 
     
     
         3 . The solid oral dosage form of  claim 1 , wherein the oral dosage form does not form an oil-in-water emulsion upon contact with water. 
     
     
         4 . The solid oral dosage form of  claim 1 , wherein the pharmaceutically acceptable carrier includes a compound selected from the group consisting of hydrophilic additives, lipophilic additives, or combinations thereof. 
     
     
         5 . The dosage form of  claim 1 , wherein the pharmaceutical carrier is not a lipid substance with chain length greater than C 12 . 
     
     
         6 . The solid oral dosage form of  claim 1 , wherein the pharmaceutically acceptable carrier includes a compound selected from the group consisting of polyvinyl alcohol, polyvinyl pyrrolidones, polyethylene glycols having molecular weight from about 100 to about 20,000; cyclodextrins; maltodextrin; hydroxypropyl methyl cellulose; carbomers; gelatin; poloxamers; ethyl alcohol; benzyl alcohol; benzyl benzoate, and combinations thereof. 
     
     
         7 . A The solid oral dosage form of  claim 1 , wherein the pharmaceutically acceptable carrier includes a compound selected from the group consisting of ethyl cellulose, cellulose acetate phthalates, glyceryl distearate, acrylic acid and methacrylic acid copolymers, methyl methacrylate copolymers, ethoxyethyl methacrylates, cyanoethyl methacrylate, aminoalkyl methacrylate copolymer, poly(acrylic acid), poly(methacrylic acid), methacrylic acid alkylamide copolymer, poly(methyl methacrylate), poly(methacrylic acid) (anhydride), methyl methacrylate, polymethacrylate, stearic acid, poly(methyl methacrylate) copolymer, polyacrylamide, aminoalkyl methacrylate copolymer, poly(methacrylic acid anhydride), and glycidyl methacrylate copolymers. 
     
     
         8 . The solid oral dosage form of  claim 4 , wherein the composition includes a hydrophilic additive that is not a hydrophilic surfactant. 
     
     
         9 . The solid oral dosage form of  claim 4 , wherein the composition includes a lipophilic additive that is not a lipophilic surfactant. 
     
     
         10 . The solid oral dosage form of  claim 4 , wherein the composition is free of triglycerides, animal and vegetable oils. 
     
     
         11 . The solid oral dosage form of  claim 1 , wherein the testosterone undecanoate is present in an amount of about 0.5 mg to about 750 mg. 
     
     
         12 . The solid oral dosage form of  claim 1 , wherein the oral dosage form is formulated for administration to a human female and the testosterone undecanoate is present in an amount of about 0.5 mg to about 200 mg. 
     
     
         13 . The solid oral dosage form of  claim 1 , wherein the oral dosage form is formulated for administration to a human male and the testosterone undecanoate is present in an amount of about 50 mg to about 750 mg. 
     
     
         14 . The solid oral dosage form of  claim 1 , wherein the oral dosage form releases about 85 wt % or less of the testosterone undecanoate in the first 30 minutes. 
     
     
         15 . The solid oral dosage form of  claim 1 , wherein the oral dosage form releases about 70% or less of the testosterone undecanoate in the first 30 minutes. 
     
     
         16 . The solid oral dosage form of  claim 1 , wherein the oral dosage form releases at least 35 wt % of the testosterone undecanoate in the first 120 minutes. 
     
     
         17 . The solid oral dosage form of  claim 1 , wherein the oral dosage form releases at least 45 wt % of the testosterone undecanoate in the first 120 minutes. 
     
     
         18 . The solid oral dosage form of  claim 1 , wherein, when administered to a human male, the oral dosage provides a dose to plasma total testosterone C avg  ratio of 4.5×10 4  dL to 4×10 6  dL. 
     
     
         19 . The solid oral dosage form of  claim 1 , wherein, when administered to a human female, the oral dosage provides a dose to plasma total testosterone C avg  ratio of 5×10 3  dL to 2×10 7  dL. 
     
     
         20 . The oral dosage capsule of  claim 1  wherein the oral dosage form upon single administration to a human subject, provides a ratio of serum testosterone undecanoate C avg  to serum total testosterone C avg  of about 3:1 to about 100:1. 
     
     
         21 . The solid oral dosage form of  claim 1 , wherein the oral dosage form has a testosterone undecanoate to pharmaceutically acceptable carrier ratio of about 8:1 (w/w) to about 1:8 (w/w). 
     
     
         22 . The solid oral dosage form of  claim 1 , wherein the oral dosage form has a testosterone undecanoate to pharmaceutically acceptable carrier ratio of about 4:1 (w/w) to about 1:4 (w/w). 
     
     
         23 . The solid oral dosage form of  claim 1 , wherein the oral dosage form is a tablet or a capsule. 
     
     
         24 . The solid oral dosage form of  claim 1 , wherein the oral dosage form is a multiparticulate oral dosage form. 
     
     
         25 . The solid oral dosage form of  claim 1 , wherein the testosterone undecanoate is present in an amorphous and/or crystalline form having a mean particle diameter of about 30 μm or less. 
     
     
         26 . The solid oral dosage form of  claim 1 , wherein, when after administration to a human male, the oral dosage form provides a plasma total testosterone C avg  of about 300 ng/dL to about 1100 ng/dL. 
     
     
         27 . The solid oral dosage form of  claim 1 , wherein, when after administration to a human male, the oral dosage form provides a plasma total testosterone C avg  of about 350 ng/dL to about 800 ng/dL. 
     
     
         28 . The solid oral dosage form of  claim 1 , wherein, when after administration to a human male, the oral dosage form provides a plasma total testosterone C avg  of about 400 ng/dL to about 600 ng/dL 
     
     
         29 . The solid oral dosage form of  claim 1 , wherein, when after administrations to a human male, the oral dosage form provides a testosterone undecanoate C avg  of about 1.5 ng/mL to about 1 μg/mL. 
     
     
         30 . The solid oral dosage form of  claim 1 , wherein, when after administrations to a human male, the oral dosage form provides a testosterone undecanoate C avg  of about 10 ng/mL to about 850 ng/mL. 
     
     
         31 . The solid oral dosage form of  claim 1 , wherein when administered to a human female, the oral dosage form provides a plasma total testosterone C avg  of about 1 ng/dL to about 100 ng/dL. 
     
     
         32 . The solid oral dosage form of  claim 1 , wherein, when administered to a human female, the oral dosage form provides a plasma total testosterone C avg  of about 20 ng/dL to about 80 ng/dL. 
     
     
         33 . The solid oral dosage form of  claim 1 , wherein, when administered to a human female, the oral dosage form provides a plasma total testosterone C avg  of about 30 ng/dL to about 70 ng/dL. 
     
     
         34 . A method of treating a subject in need of testosterone therapy, comprising:
 administering a solid oral dosage form of  claim 1  to the subject.   
     
     
         35 . The method of  claim 34  wherein the administration is done once every 24 hours. 
     
     
         36 . The method of  claim 34  wherein the administration is done once every 12 hours. 
     
     
         37 . The method of  claim 34  wherein the subject is a male and the need for testosterone therapy is associated with a condition selected from the group consisting of hypogonadism; erectile dysfunction; Klienfelter Syndrome; reduced libido; low muscle mass and low bone density; metabolic syndrome, and combinations thereof. 
     
     
         38 . The method of  claim 34  wherein the subject is a human male and the solid oral dosage form provides a daily dose of testosterone undecanoate of about 50 mg to about 1500 mg per day. 
     
     
         39 . The method of  claim 34  wherein the subject is a female and the need for testosterone therapy is associated with a condition selected from the group consisting of hypoactive sexual desire disorder, arousal disorder, dyspareunia, anorgasmia, and combinations thereof. 
     
     
         40 . The method of  claim 34  wherein the subject is a human female and the solid oral dosage form provides a daily dose of testosterone undecanoate of about 0.5 mg to about 200 mg per day.