Pharmaceutical delivery systems for hydrophobic drugs and compositions comprising same

Abstract

A drug delivery system for oral administration of hydrophobic drugs with enhanced and extended absorption and improved pharmacokinetics is provided. In one embodiment, formulations comprising testosterone and testosterone esters, e.g., testosterone palmitate, are disclosed. Methods of treating a hormone deficiency or effecting male contraception with the inventive formulations are also provided.

1 . An oral pharmaceutical formulation comprising
 about 23 wt. % or less of a testosterone ester chose from testosterone enanthate; testosterone undecanoate; testosterone cypionate, and testosterone palmitate,   about 63 wt. % of a lipophilic surfactant chosen from mono- and/or di-glycerides of fatty acids, and   about 15% of polyoxyl 40 hydrogenated castor oil.   
     
     
         2 . The oral pharmaceutical formulation of  claim 1 , wherein the testosterone ester is testosterone undecanoate. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the lipophilic surfactant is glyceryl palmitosterate, glyceryl monolinoleate, or a combination thereof. 
     
     
         4 . The oral pharmaceutical formulation of  claim 1 , wherein the lipophilic surfactant is glyceryl palmitosterate, glyceryl monolinoleate, or a combination thereof. 
     
     
         5 . An oral pharmaceutical formulation comprising
 about 23 wt. % or less of a testosterone ester selected from the group consisting of testosterone enanthate, testosterone undecanoate, testosterone cypionate, and testosterone palmitate,   about 55-65 wt. % of one or more lipophilic surfactants, and   about 15-45 wt. % of a hydrophilic surfactant having an HLB value greater than 10.   
     
     
         6 . The oral pharmaceutical formulation of  claim 5 , wherein the lipophilic surfactant is a mono- and/or di-glyceride of fatty acids. 
     
     
         7 . The oral pharmaceutical formulation of  claim 5 , wherein the lipophilic surfactant is selected from the group consisting of glyceryl caprylate/caprate, glyceryl palmitosterate, glyceryl monolinoleate and glyceryl monooleate. 
     
     
         8 . The oral pharmaceutical formulation of  claim 5 , wherein the lipophilic surfactant is chosen from transesterification products of natural or hydrogenated vegetable oil triglyceride and a polyalkylene polyol having a HLB value less than 10. 
     
     
         9 . The oral pharmaceutical formulation of  claim 8 , wherein the lipophilic surfactant is selected form the group consisting of polyoxyethylated apricot kernel oil, polyoxyethylated corn oil and polyoxyethylated hydrogenated coconut oil. 
     
     
         10 . The oral pharmaceutical formulation of  claim 5 , wherein the hydrophilic surfactant is chosen from castor oil or hydrogenated castor oil ethoxylates having a HLB value greater than 10. 
     
     
         11 . The oral pharmaceutical formulation of  claim 5 , wherein the hydrophilic surfactant is selected from the group consisting of polyoxyethylene (40) hydrogenated castor oil, polyoxyethylene (35) hydrogenated castor oil, polyoxyethylene (40) castor oil, polyoxyethylene (60) hydrogenated castor oil, polyethylene glycol 660 hydroxysterate, caprylocaproyl macrogol-8 glycerides, a-tocopherol-polyethylene glycol-1000 succinate, and ascorbyl-6 palmitate. 
     
     
         12 . The oral pharmaceutical formulation of  claim 11 , wherein the hydrophilic surfactant is polyoxyl 40 hydrogenated castor oil. 
     
     
         13 . The oral pharmaceutical formulation of  claim 11 , wherein the hydrophilic surfactant is caprylocaproyl macrogol-8 glycerides. 
     
     
         14 . The oral pharmaceutical formulation of  claim 5 , wherein the testosterone ester is testosterone undecanoate. 
     
     
         15 . The oral pharmaceutical formulation of  claim 5 , wherein the amount of testosterone ester in the formulation is about 15 wt. % thereof. 
     
     
         16 . The oral pharmaceutical formulation of  claim 5 , wherein the formulation further comprises a cosolvent which is a polyethylene glycol with an average molecular weight of about 200 to about 10,000. 
     
     
         17 . An oral pharmaceutical formulation comprising
 about 15 wt. % of a testosterone ester selected from the group consisting of testosterone enanthate, testosterone undecanoate, testosterone cypionate, and testosterone palmitate,   about 65 wt. % of a surfactant selected from mono- and/or di-glycerides of fatty acids, and   about 17.5 wt. % of polyoxyl 40 hydrogenated castor oil.