Process for preparing concentrated aqueous micellar solutions

Abstract

The present invention provides a method for preparing supersaturated aqueous solutions of micelles of compounds in which the solubility in water is less than the critical micelle concentration. The solutions can be process to prepare solid micelles which have advantageous properties for drug delivery.

1 . A process for preparing a supersaturated aqueous solution of micelles from an amphiphilic compound whose solubility product (K sp ) in water is less than the critical micelle concentration (CMC) in water which process comprises the steps of:
 (a) dissolving an amphiphilic compound in a water miscible organic solvent;   (b) adding water, and optionally a stoichiometric quantity of aqueous alkaline or alkali metal hydroxide or aqueous acid to form a salt, to provide a homogenous mixed aqueous solvent system; and,   (c) heating the solution under reduced pressure at a temperature which results in distillation of the organic solvent to produce a supersaturated aqueous solution of micelles containing less than 0.5% of the organic solvent.   
   
   
       2 . A process according to  claim 1  further comprising the step of spray drying the resulting solution to afford a stable amorphous solid micelle. 
   
   
       3 . A process according to  claim 1  further comprising the step of lyophilizing the resulting solution to afford a stable amorphous solid. 
   
   
       4 . A process according to  claim 1  wherein:
 said compound is a compound of formula I:   
     
       
         
         
             
             
         
       
       said organic solvent is tetrahydrofuran (THF); 
       two equivalents of 1 M NaOH are added. 
     
   
   
       5 . A process according to  claim 4  further comprising the step of spray drying the aqueous micelle solution to afford a stable amorphous micellar solid. 
   
   
       6 . A process according to  claim 1  wherein:
 said compound is a compound of formula II; and,   
     
       
         
         
             
             
         
       
       said solvent is iso-propanol (IPA) 
     
   
   
       7 . A process according to  claim 6  further comprising the step of spray drying the aqueous micelle solution to afford a stable amorphous micellar solid.