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 .- 213 . (canceled) 
     
     
         214 . An oral pharmaceutical composition comprising (1) a testosterone ester chosen from testosterone enanthate; testosterone undecanoate; testosterone cypionate, and testosterone palmitate, (2) a lipophilic surfactant chosen from mono- and/or di-glycerides of fatty acids, (3) Cremophor RH40 (polyoxyl 40 hydrogenated castor oil), and (4) a polyethylene glycol with an average molecular weight of about 200 to about 10,000 g/mol, wherein said composition is a semi-solid. 
     
     
         215 . The pharmaceutical composition as recited in  claim 214  wherein the testosterone ester is testosterone undecanoate. 
     
     
         216 . The composition as recited in  claim 214  wherein said mono and/or di-glycerides of fatty acids is chosen from Precirol ATO 5 (glyceryl palmitostearate) and Maisine (glyceryl mono-linoleate). 
     
     
         217 . The composition as recited in  claim 214  wherein said composition contains 10% to 20% w/w of testosterone ester. 
     
     
         218 . The composition as recited in  claim 214  wherein said composition is free of ethanol. 
     
     
         219 . A method of treating testosterone deficiency or its symptoms comprising orally administering to a subject suffering from testosterone deficiency or its symptoms an effective amount of a pharmaceutical composition comprising (1) a testosterone ester chosen from testosterone enanthate; testosterone undecanoate; testosterone cypionate, and testosterone palmitate, (2) a lipophilic surfactant chosen from mono- and/or di-glycerides of fatty acids, (3) Cremophor RH40 (polyoxyl 40 hydrogenated castor oil), and (4) a polyethylene glycol with an average molecular weight of about 200 to about 10,000 g/mol, wherein said composition is a semi-solid. 
     
     
         220 . The method as recited in  claim 219  wherein the testosterone ester is testosterone undecanoate. 
     
     
         221 . The method as recited in  claim 219  wherein said mono and/or di-glycerides of fatty acids is chosen from Precirol ATO 5 (glyceryl palmitostearate) and Maisine (glyceryl mono-linoleate). 
     
     
         222 . The method as recited in  claim 219  wherein said composition contains 10% to 20% w/w of testosterone ester. 
     
     
         223 . The method as recited in  claim 219  wherein said composition is free of ethanol.