Novel Method for Producing Nanocapsules in the Absence of an Organic Solvent, and Nanocapsules Produced Thereby

Abstract

The invention relates to a method for preparing an aqueous suspension of nanocapsules comprising an oily core surrounded by a polymeric shell, in which method the following phases are mixed: a) a first phase, called an oily phase, comprising: a hydrophobic polymer, an oil or a mixture of oils, at least one active ingredient, and a surfactant TA 1 , this oily phase being brought to a temperature T 1 higher than the melting point of the hydrophobic polymer, the hydrophobic polymer being miscible, at this temperature T 1 , with the mixture of the surfactant TA 1 and the oil or mixture of oils, and the active ingredient being miscible, soluble or solubilized in the mixture of the surfactant TA 1 and the oil or mixture of oils; b) a second phase, called a polar phase, comprising a hydrophilic polymer in the form of a hydrogel in an aqueous solution containing a surfactant TA 2 , in such a way as to obtain the formation of the nanocapsules in an aqueous suspension.

1 - A method for preparing an aqueous suspension of nanocapsules comprising an oily core surrounded by a polymeric shell, in which method the following phases are mixed:
 a) a first phase, called an oily phase, comprising:
 a hydrophobic polymer, 
 an oil or a mixture of oils, 
 at least one active ingredient, 
 and a surfactant TA 1 , 
 this oily phase being brought to a temperature T 1  higher than the melting point of the hydrophobic polymer, the hydrophobic polymer being miscible, at this temperature T 1 , with the mixture of the surfactant TA 1  and the oil or mixture of oils, and the active ingredient being miscible, soluble or solubilized in the mixture of the surfactant TA 1  and the oil or mixture of oils; 
   b) a second phase, called a polar phase, comprising a hydrophilic polymer in the form of a hydrogel in an aqueous solution containing a surfactant TA 2 ,   
       in such a way as to obtain the formation of the nanocapsules in an aqueous suspension. 
     
     
         2 - The method as claimed in  claim 1 , characterized in that the mixing of the two phases is carried out by adding the polar phase to the oily phase, with stirring. 
     
     
         3 - The method as claimed in  claim 1 , characterized in that the polar phase is brought to a temperature T 2  which is 2 to 5° C. lower than the melting point of the hydrophobic polymer. 
     
     
         4 - The method as claimed in  claim 1 , characterized in that the active ingredient is miscible, soluble or solubilized in the mixture of the surfactant TA 1  and the oil or mixture of oils, at ambient temperature, in particular at 20° C. 
     
     
         5 - The method as claimed in  claim 1 , characterized in that the oil or the mixture of oils has an HLB included in the range of from 3 to 6. 
     
     
         6 - The method as claimed in  claim 1 , characterized in that the active ingredient is chosen from pharmaceutical or cosmetic active agents. 
     
     
         7 - The method as claimed in  claim 1 , characterized in that the oil(s) is (are) preferably chosen from triglycerides, in particular medium-chain triglycerides, propylene glycol dicaprylocaprates, and oleoyl, lauroyl and linoleoyl macrogolglycerides. 
     
     
         8 - The method as claimed in  claim 1 , characterized in that the surfactant TA 1  has an HLB included in the range of from 3 to 6, and is preferably chosen from propylene glycol laurates, propylene glycol caprylates, polyglyceryl oleates and caprylocaproyl macrogolglycerides. 
     
     
         9 - The method as claimed in  claim 1 , characterized in that the hydrophobic polymer is chosen from vinyl polymers, polyesters, polyamides, polyurethanes and polycarbonates, which preferably have a melting point lower than 120° C., such as poly-ε-caprolactones. 
     
     
         10 - The method as claimed in  claim 1 , characterized in that the hydrophilic polymer is chosen from synthetic cellulosic derivatives, preferably from cellulose ethers, such as methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, methylethylcellulose and sodium carboxymethylcellulose. 
     
     
         11 - The method as claimed in  claim 1 , characterized in that the surfactant TA 2  has an HLB of greater than or equal to 15, and is preferably chosen from neutral surfactants. 
     
     
         12 - The method as claimed in  claim 1 , characterized in that the oily phase comprises from 5% to 20% by mass, preferably from 8% to 12% by mass, of hydrophobic polymer. 
     
     
         13 - The method as claimed in  claim 1 , characterized in that the oily phase advantageously comprises from 5% to 20% by mass, preferably from 8% to 12% by mass, of oil or mixture of oils. 
     
     
         14 - The method as claimed in  claim 1 , characterized in that the oily phase comprises from 0.5% to 5% by mass, preferably from 1% to 3% by mass, of active ingredient. 
     
     
         15 - The method as claimed in  claim 1 , characterized in that the oily phase comprises from 55% to 89.5% by mass, preferably from 73% to 83% by mass, of surfactant TA 1 . 
     
     
         16 - The method as claimed in  claim 1 , characterized in that the polar phase comprises from 0.1% to 5% by mass, preferably from 0.15% to 2% by mass, of hydrophilic polymer. 
     
     
         17 - The method as claimed in  claim 1 , characterized in that the polar phase comprises from 90% to 99.8% by mass, preferably from 96% to 99.65% by mass, of water or of a water/polar solvents mixture. 
     
     
         18 - The method as claimed in  claim 1 , characterized in that the polar phase comprises from 0.1% to 5% by mass, preferably from 0.2% to 2% by mass, of surfactant TA 2 . 
     
     
         19 - The method as claimed in  claim 1 , characterized in that the hydrophobic polymer/hydrophilic polymer mass ratio is less than or equal to 0.4. 
     
     
         20 - The method as claimed in  claim 1 , characterized in that the nanocapsules obtained have a diameter included in the range of from 200 to 1000 nm, preferably in the range of from 300 to 500 nm. 
     
     
         21 - Nanocapsules comprising an oily core in which an active ingredient is homogeneously dispersed and a polymeric shell formed from a hydrophobic polymer and from a hydrophilic polymer, which can be obtained according to the method as defined in  claim 1 . 
     
     
         22 - The nanocapsules as claimed in  claim 21 , characterized in that the hydrophilic polymer forms a protective colloid which coats or is entangled with the hydrophobic polymer forming the shell of the nanocapsules. 
     
     
         23 - An aqueous suspension of nanocapsules as claimed in  claim 21 . 
     
     
         24 - Pharmaceutical or cosmetic or food compositions, comprising nanocapsules as claimed in  claim 21  or an aqueous suspension of said nanocapsules in combination with at least one pharmaceutically or physiologically acceptable excipient.