Taxane Pro-Emulsion Formulations and Methods Making and Using the Same

Abstract

Taxane pro-emulsion formulations are provided. Pro-emulsion formulations are dried powders that include a taxane, oil, surfactant and sugar alcohol. Also provided are methods of making and using the pro-emulsion formulations, as well as kits that include the pro-emulsion formulations.

1 . A taxane pro-emulsion formulation comprising:
 a taxane;   an oil;   a surfactant; and   a sugar alcohol;   wherein the formulation is formulated to produce upon combination with an aqueous medium a clear emulsion having a particle size that is substantially the same as that of the precursor emulsion.   
     
     
         2 . The pro-emulsion formulation according to  claim 1 , wherein the taxane is described by the formula: 
       
         
           
           
               
               
           
         
         R 3 =alkyl of 1 to 6 carbons or phenyl; and 
         R 4 =alkyl of 1 to 6 carbons or phenyl. 
       
     
     
         3 . The pro-emulsion formulation according to  claim 2 , wherein the taxane is paclitaxel. 
     
     
         4 . The pro-emulsion formulation according to  claim 2 , wherein the taxane is docetaxel. 
     
     
         5 . The pro-emulsion formulation according to  claim 1 , wherein the oil is present in an amount ranging from 0.1 to 10% by weight. 
     
     
         6 . The pro-emulsion formulation according to  claim 5 , wherein the oil is selected from the group consisting of soybean oil, a tocopherol and a glycerol ester of a medium chain fatty acid. 
     
     
         7 . The pro-emulsion formulation according to  claim 1 , wherein the surfactant is present in an amount ranging from 10 to 70% by weight. 
     
     
         8 . The pro-emulsion formulation according to  claim 7 , wherein the surfactant is a non-ionic surfactant. 
     
     
         9 . The pro-emulsion formulation according to  claim 8 , wherein the non-ionic surfactant is polysorbate 80. 
     
     
         10 . The pro-emulsion formulation according to  claim 1 , wherein the pro-emulsion formulation includes a non-aqueous solvent. 
     
     
         11 . The pro-emulsion formulation according to  claim 10 , wherein the non-aqueous solvent is present in an amount ranging from 0.1 to 30% by weight. 
     
     
         12 . The pro-emulsion formulation according to  claim 10 , wherein the non-aqueous solvent is proplyene glycol. 
     
     
         13 . The pro-emulsion formulation according to  claim 1 , wherein the sugar alcohol is present in an amount ranging from 15 to 80% dry weight. 
     
     
         14 . The pro-emulsion formulation according to  claim 12 , wherein the sugar alcohol is mannitol. 
     
     
         15 . The pro-emulsion formulation according to  claim 1 , wherein the pro-emulsion formulation further comprises an emulsification enhancer. 
     
     
         16 . The pro-emulsion formulation according to  claim 15 , wherein the emulsification enhancer is oleic acid. 
     
     
         17 . The pro-emulsion formulation according to  claim 1 , wherein the particle size is 70 nm or less. 
     
     
         18 . A taxane pro-emulsion formulation comprising:
 a taxane;   soybean oil;   polysorbate 80;   propylene glycol; and   mannitol;   wherein the formulation is formulated to produce upon combination with an aqueous medium clear emulsion having a particle size that is substantially the same as that of the precursor emulsion.   
     
     
         19 . The pro-emulsion formulation according to  claim 18 , wherein the taxane is paclitaxel. 
     
     
         20 . The pro-emulsion formulation according to  claim 18 , wherein the taxane is docetaxel. 
     
     
         21 . The pro-emulsion formulation according to  claim 18 , wherein the soybean oil is present in an amount ranging from 0.4 to 8% by weight. 
     
     
         22 . The pro-emulsion formulation according to  claim 18 , wherein the polysorbate 80 is present in an amount ranging from 30 to 60% by weight. 
     
     
         23 . The pro-emulsion formulation according to  claim 18 , wherein the propylene glycol is present in an amount ranging from 0.1 to 15% by weight. 
     
     
         24 . The pro-emulsion formulation according to  claim 18 , wherein the mannitol is present in an amount ranging from 25 to 65% dry weight. 
     
     
         25 . The pro-emulsion formulation according to  claim 18 , wherein the pro-emulsion formulation further comprises oleic acid. 
     
     
         26 . A method of administering a taxane to a subject, the method comprising:
 (a) combining a taxane pro-emulsion formulation according to  claim 1  with an aqueous medium to produce a clear taxane emulsion; and   (b) administering the taxane emulsion to the subject.   
     
     
         27 - 44 . (canceled) 
     
     
         45 . A clear taxane emulsion comprising:
 a taxane;   oil;   a surfactant;   a sugar alcohol; and   water.   
     
     
         46 - 78 . (canceled)