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 .- 228 . (canceled) 
     
     
         229 . An oral pharmaceutical composition comprising (1) a medium-chain (C 7 -C 13 ) fatty acid testosterone ester, (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. 
     
     
         230 . The pharmaceutical composition as recited in  claim 229  wherein the testosterone ester is testosterone undecanoate. 
     
     
         231 . The composition as recited in  claim 229  wherein said mono and/or di-glycerides of fatty acids is chosen from Precirol ATO 5 (glyceryl palmitostearate) and Maisine (glyceryl mono-linoleate). 
     
     
         232 . The composition as recited in  claim 229  wherein said composition contains 10% to 20% w/w of testosterone ester. 
     
     
         233 . The composition as recited in  claim 229  wherein said composition is free of ethanol. 
     
     
         234 . 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 229 . 
     
     
         235 . The method as recited in  claim 234  wherein the testosterone ester is testosterone undecanoate. 
     
     
         236 . The method as recited in  claim 234  wherein said mono and/or di-glycerides of fatty acids is chosen from Precirol ATO 5 (glyceryl palmitostearate) and Maisine (glyceryl mono-linoleate). 
     
     
         237 . The method as recited in  claim 234  wherein said composition contains 10% to 20% w/w of testosterone ester. 
     
     
         238 . The method as recited in  claim 234  wherein said composition is free of ethanol. 
     
     
         239 . An oral pharmaceutical composition comprising (1) a medium-chain (C 7 -C 13 ) fatty acid testosterone ester, (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 free of ethanol. 
     
     
         240 . The pharmaceutical composition as recited in  claim 239  wherein the testosterone ester is testosterone undecanoate. 
     
     
         241 . The composition as recited in  claim 239  wherein said mono and/or di-glycerides of fatty acids is chosen from Precirol ATO 5 (glyceryl palmitostearate) and Maisine (glyceryl mono-linoleate). 
     
     
         242 . The composition as recited in  claim 239  wherein said composition contains 10% to 20% w/w of testosterone ester. 
     
     
         243 . The composition as recited in  claim 239  wherein said composition is a semi-solid. 
     
     
         244 . 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 239 . 
     
     
         245 . The method as recited in  claim 244  wherein the testosterone ester is testosterone undecanoate. 
     
     
         246 . The method as recited in  claim 244  wherein said mono and/or di-glycerides of fatty acids is chosen from Precirol ATO 5 (glyceryl palmitostearate) and Maisine (glyceryl mono-linoleate). 
     
     
         247 . The method as recited in  claim 244  wherein said composition contains 10% to 20% w/w of testosterone ester. 
     
     
         248 . The method as recited in  claim 244  wherein said composition is a semi-solid.