Emulsion vehicle for poorly soluble drugs

Abstract

An emulsion of α-tocopherol, stabilized by biocompatible surfactants, as a vehicle or carrier for therapeutic drugs, which is substantially ethanol free and which can be administered to animals or humans various routes is disclosed. Also included in the emulsion is PEGylated vitamin E. PEGylated α-tocopherol includes polyethylene glycol subunits attached by a succinic acid diester at the ring hydroxyl of vitamin E and serves as a primary surfactant, stabilizer and a secondary solvent in emulsions of α-tocopherol.

We claim:  
     
         1 . A pharmaceutical composition, comprising: 
 α-tocopherol,    one or more surfactants,    an aqueous phase, and    a therapeutic agent    wherein said composition is in the form of an emulsion or micellar solution.    
     
     
         2 . The composition of  claim 1  wherein said surfactant is an α-tocopherol derivative.  
     
     
         3 . The composition of  claim 2  wherein said vitamin E derivative is an ester or an ether of α-tocopherol and polyethylene glycol.  
     
     
         4 . The composition of  claim 2  wherein said vitamin E derivative is TPGS.  
     
     
         5 . The composition of  claim 4  wherein the ratio of α-tocopherol to TPGS is from about 1:1 to about 10:1 w/w.  
     
     
         6 . The composition of  claim 5  further including a second surfactant wherein said second surfactant has an HLB of at least 10.  
     
     
         7 . The composition of  claim 6  wherein said second surfactant is selected from the group consisting of anionic, cationic, nonionic and zwitterionic surfactants.  
     
     
         8 . The composition of  claim 7  wherein said second surfactant is selected from the group consisting of poloxypropylene-polyoxyethylene glycol nonionic block poplymers, ascorbyl-6-palmitate, stearylamine and sucrose fatty esters.  
     
     
         9 . The composition of  claim 8  wherein said second surfactant is ascorbyl-6-palmitate.  
     
     
         10 . The composition of  claim 8  wherein said second surfactant has a structure: 
       OH (OCH 2 CH 2 ) a  (OCH 2 CH 2 CH 2 ) b  (OCH 2 CH 2 ) a  H 
       wherein a is 101 and b is 56.  
     
     
         11 . The composition of  claim 1  wherein said therapeutic agent is a chemotherapeutic agent.  
     
     
         12 . The composition of  claim 11  wherein said chemotherapeutic is a taxoid molecule.  
     
     
         13 . The composition of  claim 12  wherein said taxoid molecule is paclitaxel.  
     
     
         14 . The composition of  claim 1  wherein the particle size of said emulsion is 10 to 500 nm.  
     
     
         15 . A pharmaceutical composition, comprising: 
 α-tocopherol,    one or more surfactants, and    a therapeutic agent    wherein said composition is in the form of a self-emulsifying drug delivery system and wherein said composition is substantially ethanol free.    
     
     
         16 . The composition of  claim 15  wherein said therapeutic agent is a chemotherapeutic agent.  
     
     
         17 . The composition of  claim 6  wherein said chemotherapeutic agent is a taxoid molecule.  
     
     
         18 . The composition of  claim 7  wherein said taxoid molecule is paclitaxel.  
     
     
         19 . The composition of  claim 15  wherein said surfactant is a vitamin E derivative.  
     
     
         20 . The composition of  claim 19  wherein said vitamin E derivative is an ester or an ether of vitamin E and polyethylene glycol.  
     
     
         21 . The composition of  claim 19  wherein said vitamin E derivative is TPGS.  
     
     
         22 . The composition of  claim 21  wherein the ratio of α-tocopherol to TPGS is from about 1:1 to about 10:1 w/w.  
     
     
         23 . The composition of  claim 15  wherein the particle size of said self-emulsifying drug delivery system is from about 10 to about 500 nm.  
     
     
         24 . A method of making an emulsion, comprising: 
 a) dissolving a therapeutic agent in ethanol, to form a therapeutic agent solution;    b) adding α-tocopherol to said therapeutic agent solution to form an α-tocopherol therapeutic agent solution;    c) removing said ethanol from said α-tocopherol therapeutic agent solution to reduce the ethanol concentration to less than 0.3% therein;    d) blending said substantially ethanol-free therapeutic agent solution with a surfactant to form a pre-emulsion; and    e) homogenizing said pre-emulsion to form an emulsion.