Non-aqueous taxane pro-emulsion formulations and methods of making and using the same

Abstract

Non-aqueous taxane pro-emulsion formulations are provided. Pro-emulsion formulations of embodiments of the invention include a taxane, an oil component, a surfactant component and, optionally, a non-aqueous solvent component. Also provided are methods of making and using the pro-emulsion formulations, as well as kits that include the pro-emulsion formulations.

1 . A non-aqueous docetaxel liquid pro-emulsion formulation comprising:
 anhydrous docetaxel or a hydrate thereof;   an organic acid selected from the group consisting of lactic acid, acetic acid and citric acid;   an oil component, wherein the oil is present in an amount ranging from 0.1 to 10% w/w;   a non-aqueous solvent selected from the group consisting of propylene glycol, glycerin, polyethylene glycol, wherein the non-aqueous solvent is present in an amount ranging from 15 to 65% w/w; and   a non-ionic surfactant component, wherein the non-ionic surfactant is present in an amount ranging from 30 to 70% w/w.   
     
     
         2 . The pro-emulsion formulation according to  claim 1 , wherein the docetaxel is anhydrous docetaxel. 
     
     
         3 . The pro-emulsion formulation according to  claim 1 , wherein the docetaxel is docetaxel trihydrate. 
     
     
         4 . The pro-emulsion formulation according to  claim 1 , wherein the oil component is present in an amount ranging from 0.3 to 5% w/w. 
     
     
         5 . The pro-emulsion formulation according to  claim 4 , wherein the oil is selected from the group consisting of synthetic oils, vegetable oils, tocopherols and combinations thereof. 
     
     
         6 . The pro-emulsion formulation according to  claim 4 , wherein the oil is selected from the group consisting of soybean oil, olive oil, sesame oil, corn oil, a medium chain triglyceride, a tocopherol or derivative thereof, and combinations thereof. 
     
     
         7 . The pro-emulsion formulation according to  claim 1 , wherein the amounts of the docetaxel and oil components differ by 50% w/w or less. 
     
     
         8 . The pro-emulsion formulation according to  claim 7 , wherein the amounts of the docetaxel and oil components differ by 10% w/w or less. 
     
     
         9 . The pro-emulsion formulation according to  claim 1 , wherein the non-ionic surfactant is polysorbate 80. 
     
     
         10 . The pro-emulsion formulation according to  claim 1 , wherein the non-aqueous solvent component is polyethylene glycol. 
     
     
         11 . The pro-emulsion formulation according to  claim 1 , wherein the organic acid is lactic acid. 
     
     
         12 . The pro-emulsion formulation according to  claim 11 , wherein the lactic acid is present in an amount ranging from 0.3 to 3% w/w. 
     
     
         13 . The pro-emulsion formulation according to  claim 1 , wherein the particle size of the formulation ranges from 3 to 70 nm. 
     
     
         14 . The pro-emulsion formulation according to  claim 1 , wherein the particle size of the formulation ranges from 8 to 15 nm. 
     
     
         15 . A non-aqueous docetaxel liquid pro-emulsion formulation comprising:
 anhydrous docetaxel or a hydrate thereof;   
       an organic acid selected from the group consisting of lactic acid, acetic acid and citric acid, wherein the organic acid is present in an amount ranging from 0.3 to 3% w/w;
 an oil component selected from the group consisting of soybean oil, olive oil, sesame oil, corn oil, a medium chain triglyceride, a tocopherol or derivative thereof, and combinations thereof, wherein the oil component is present in an amount ranging from 0.3 to 5% w/w; 
 polyethylene glycol having an average molecular weight of 1,000, present in an amount ranging from 30 to 60% w/w; and 
 a non-ionic surfactant component, wherein the non-ionic surfactant is present in an amount ranging from 30 to 60% w/w. 
 
     
     
         16 . The pro-emulsion formulation according to  claim 15 , wherein the is anhydrous docetaxel. 
     
     
         17 . The pro-emulsion formulation according to  claim 15 , wherein the docetaxel is docetaxel trihydrate. 
     
     
         18 . The pro-emulsion formulation according to  claim 15 , wherein the oil is soybean oil. 
     
     
         19 . The pro-emulsion formulation according to  claim 15 , wherein the oil is a medium chain triglyceride. 
     
     
         20 . The pro-emulsion formulation according to  claim 15 , wherein the amounts of the docetaxel and oil differ by 50% w/w or less. 
     
     
         21 . The pro-emulsion formulation according to  claim 15 , wherein the amounts of the docetaxel and oil differ by 10% w/w or less. 
     
     
         22 . The pro-emulsion formulation according to  claim 15 , wherein the non-ionic surfactant is polysorbate 80. 
     
     
         23 . The pro-emulsion formulation according to  claim 15 , wherein the organic acid is lactic acid. 
     
     
         24 . The pro-emulsion formulation according to  claim 15 , wherein the particle size of the formulation ranges from 8 to 15 nm. 
     
     
         25 . A method of administering docetaxel to a subject, the method comprising:
 (a) combining the pro-emulsion formulation according to  claim 1  with an aqueous medium to produce a docetaxel emulsion; and   (b) administering the docetaxel emulsion to the subject.   
     
     
         26 . A kit comprising:
 (a) the pro-emulsion formulation according to  claim 1 ; and   (b) an aqueous medium.