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 .- 248 . (canceled) 
     
     
         249 . 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 a fatty acid and mono- and/or di-glycerides of fatty acids; and (3) a hydrophilic surfactant;
 wherein said composition is a semi-solid;   wherein said composition releases about 90% or less of said testosterone ester after 30 minutes in phosphate buffer solution;   the pharmaceutical composition providing an average steady state serum level of total testosterone within a range of about 300 ng/dl to about 1100 ng/dl when administered twice daily to a patient in need of testosterone therapy.   
     
     
         250 . The pharmaceutical composition as recited in  claim 249  wherein the testosterone ester is testosterone undecanoate. 
     
     
         251 . The pharmaceutical composition as recited in  claim 249  wherein the lipophilic surfactant is a fatty acid. 
     
     
         252 . The pharmaceutical composition as recited in  claim 251  wherein the fatty acid is oleic acid. 
     
     
         253 . The pharmaceutical composition as recited in  claim 249  wherein the lipophilic surfactant is mono- and/or di-glycerides of fatty acids. 
     
     
         254 . The composition as recited in  claim 253  wherein said mono and/or di-glycerides of fatty acids is chosen from Precirol ATO 5 (glyceryl palmitostearate) and Maisine (glyceryl mono-linoleate). 
     
     
         255 . The pharmaceutical composition as recited in  claim 249  wherein the hydrophilic surfactant is Cremophor RH40 (polyoxyl 40 hydrogenated castor oil). 
     
     
         256 . The composition as recited in  claim 249  wherein said composition is a semi-solid. 
     
     
         257 . 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 as recited in  claim 249 . 
     
     
         258 . The method as recited in  claim 257  wherein the testosterone ester is testosterone undecanoate. 
     
     
         259 . The method as recited in  claim 257  wherein the lipophilic surfactant is a fatty acid. 
     
     
         260 . The method as recited in  claim 259  wherein the fatty acid is oleic acid. 
     
     
         261 . The method as recited in  claim 257  wherein the lipophilic surfactant is mono and/or di-glycerides of fatty acids. 
     
     
         262 . The method as recited in  claim 261  wherein said mono and/or di-glycerides of fatty acids is chosen from Precirol ATO 5 (glyceryl palmitostearate) and Maisine (glyceryl mono-linoleate). 
     
     
         263 . The pharmaceutical composition as recited in  claim 249  wherein the hydrophilic surfactant is Cremophor RH40 (polyoxyl 40 hydrogenated castor oil). 
     
     
         264 . The composition as recited in  claim 249  wherein said composition is free of ethanol.