Emulsion vehicle for poorly soluble drugs

Abstract

An emulsion of tocopherol incorporating a co-solvent and, 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 by 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: 
 one or more tocopherols or derivatives thereof,    a co-solvent,    one or more surfactants,    an aqueous phase, and    a chemotherapeutic agent selected from taxoids, taxines, microtubule-binding agents, and taxanes,    wherein said composition is in the form of an emulsion or micellar solution and is essentially free of any monohydric alcohol.    
     
     
         2 . The composition of  claim 1  wherein said co-solvent is selected from dimethylsulfoxide, dimethylamide, ethylene glycol, propylene glycol, glycerol, sorbitol, mannitol, polyethylene glycol, N-methyl-2-pyrrolidone, polyvinyl-pyrrolidone or mixtures thereof.  
     
     
         3 . The composition of  claim 1  wherein said surfactant is an α-tocopherol derivative.  
     
     
         4 . The composition of  claim 2  wherein said polyethylene glycol has a molecular weight between 100 to 10,000.  
     
     
         5 . The composition of  claim 1  wherein said tocopherol is selected from α-tocotrienol, β-tocotrienol, γ-tocotrienol, δ-tocotrienol, α-tocopherol, α-tocopherol acetate, α-tocopherol phosphate, α-tocopherol succinate, α-tocopherol nicotinate, and α-tocopherol linoleate.  
     
     
         6 . The composition of  claim 2  wherein said co-solvent is N-methyl-2-pyrrolidone.  
     
     
         7 . The composition of  claim 3  wherein said α-tocopherol derivative is an ester or an ether of α-tocopherol and polyethylene glycol.  
     
     
         8 . The composition of  claim 3  wherein said α-tocopherol derivative is D-α-tocopherol-polyethylene glycol 1000 succinate.  
     
     
         9 . The composition of  claim 8  wherein the ratio of α-tocopherol to D-α-tocopherol-polyethylene glycol 1000 succinate is from 1:1 to 10:1 w/w.  
     
     
         10 . The composition of  claim 9  further including a second surfactant wherein said second surfactant has an HLB of at least 10.  
     
     
         11 . The composition of  claim 10  wherein said second surfactant is selected from the group consisting of anionic, cationic, nonionic and zwitterionic surfactants.  
     
     
         12 . The composition of  claim 10  wherein said second surfactant is selected from the group of poloxypropylene-polyoxyethylene glycol nonionic block polymers, ascorbyl-6-palmitate, stearylamine and sucrose fatty esters.  
     
     
         13 . The composition of  claim 10  wherein said second surfactant is pegylated.  
     
     
         14 . The composition of  claim 10  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.  
     
     
         15 . The composition of  claim 1  wherein said taxane is paclitaxel.  
     
     
         16 . The composition of  claim 15  wherein said taxane derivative is selected from a benzoate derivative of paclitaxel, 2-debenzoyl-2-aroyl, 7 deoxytaxol, docetaxol and C-2-acetoxy-C-4-benzoate paclitaxel.  
     
     
         17 . The composition of  claim 16  wherein said taxane derivative is C-4-aziridine paclitaxel.  
     
     
         18 . The composition of  claim 16  wherein said taxane derivative is 7-deoxytaxol.  
     
     
         19 . The composition of  claim 1  wherein said taxane is docetaxel.  
     
     
         20 . The composition of  claim 1  where said monohydric alcohol is selected from ethanol, butanol, isopropanol or mixtures thereof.  
     
     
         21 . A pharmaceutical composition comprising: 
 α-tocopherol,    D-α-tocopherol polyethyleneglycol 1000 succinate as a first surfactant,    a second surfactant,    an aqueous phase,    a co-solvent, and a chemotherapeutic agent selected from taxoids,    taxines, taxanes, and microtubule-stabilizing agents, wherein said composition is in the form of an emulsion or micellar solution.    
     
     
         22 . The composition of  claim 21  wherein said taxane is paclitaxel.  
     
     
         23 . The composition of  claim 21  wherein said co-solvent is selected from dimethylsulfoxide, dimethylamide, ethylene glycol, propylene glycol, glycerol, sorbitol, mannitol, polyethylene glycol, N-methyl-2-pyrrolidone, polyvinyl-pyrrolidone or mixtures thereof.  
     
     
         24 . The composition of  claim 21  wherein said second surfactant is selected from the group of poloxypropylene-polyoxyethylene glycol nonionic block polymers, ascorbyl-6-palmitate, stearylamine and sucrose fatty esters.