Pharmaceutical delivery systems for hydrophobic drugs and compositions 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 .- 193 . (canceled) 
     
     
         194 . An oral pharmaceutical composition comprising (1) a testosterone ester having the structure: 
       
         
           
           
               
               
           
         
       
       wherein R is chosen from —C(O)C 12 H 25  and —C(O)C 13 H 27 , and one or both esters can be present in the oral pharmaceutical composition, (2) a lipophilic surfactant, and (3) a hydrophilic surfactant. 
     
     
         195 . The composition as recited in  claim 194 , wherein R is —C(O)C 12 H 25 . 
     
     
         196 . The composition as recited in  claim 194 , wherein R is —C(O)C 13 H 27 . 
     
     
         197 . The composition as recited in  claim 194 , wherein said formulation further comprises a polyethylene glycol with an average molecular weight of about 200 to about 10,000. 
     
     
         198 . The composition as recited in  claim 194 , wherein said lipophilic surfactant is chosen from fatty acids and mono- and/or di-glycerides of fatty acids and propylene glycol mono- and/or di-esters of fatty acids. 
     
     
         199 . The composition as recited in  claim 198  wherein said mono and/or di-glycerides of fatty acids is chosen from Precirol ATO 5 (glyceryl palmitostearate), Imwitor 191 (glyceryl monostearate), Peceol (glyceryl mono-oleate), Softigen 701 (glyceryl mono-/di-ricinoleate), Capmul MCM (glyceryl caprylate/caprate), and Maisine (glyceryl mono-linoleate). 
     
     
         200 . The composition as recited in  claim 198  wherein said propylene glycol mono and/or di-esters of fatty acids is chosen from Captex 200 (propylene glycol dicaprylate/dicaprate) and Lauroglycol (propylene glycol monolaurate). 
     
     
         201 . The composition as recited in  claim 194 , wherein said hydrophilic surfactant is chosen from a polyoxyethylene sorbitan fatty acid derivative and a hydrogenated castor oil ethoxylate. 
     
     
         202 . The composition as recited in  claim 201 , wherein said hydrogenated castor oil ethoxylate is chosen from Tween 80 (polysorbate 80), Cremophor RH40 (polyoxyl 40 hydrogenated castor oil), and Labrasol (caprylocaproylmacrogol-8-glycerides). 
     
     
         203 . The composition as recited in  claim 194 , wherein said composition is free of ethanol. 
     
     
         204 . The composition as recited in  claim 194 , wherein said composition contains 10% to 30% w/w of testosterone ester. 
     
     
         205 . The composition as recited in  claim 204 , wherein said composition contains 10% to 20% w/w of testosterone ester. 
     
     
         206 . An oral pharmaceutical composition consisting essentially of (1) a testosterone ester having the structure: 
       
         
           
           
               
               
           
         
       
       wherein R is chosen from —C(O)C 12 H 25  and —C(O)C 13 H 27 , and one or both esters can be present in the oral pharmaceutical composition, (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. 
     
     
         207 . The composition as recited in  claim 206 , wherein R is —C(O)C 12 H 25 . 
     
     
         208 . The composition as recited in  claim 206 , wherein R is —C(O)C 13 H 27 . 
     
     
         209 . The composition as recited in  claim 206  wherein said mono and/or di-glycerides of fatty acids is chosen from Precirol ATO 5 (glyceryl palmitostearate), and Maisine (glyceryl mono-linoleate). 
     
     
         210 . The composition as recited in  claim 206 , wherein said composition contains 10% to 20% w/w of testosterone ester. 
     
     
         211 . The composition of  claim 206 , wherein said mono- and/or di-glycerides of fatty acids has a melting point above room temperature. 
     
     
         212 . The composition of  claim 211 , wherein said mono- and/or di-glycerides of fatty acids has a melting point from about 35° C. to about 65° C. 
     
     
         213 . The pharmaceutical composition of  claim 211  wherein said composition is semi-solid at room temperature. 
     
     
         214 . The composition of  claim 194 , wherein said mono- and/or di-glycerides of fatty acids has a melting point above room temperature.