Utilization of a transacylation reaction between an esterified polysaccharide and a polyaminated or polyhydroxylated substance for fabricating microparticles, microparticles thus obtained, methods and compositions containing them

A process for the manufacture of microparticles, which comprises the following successive steps:

• a) preparing a substantially neutral aqueous solution containing a polysaccharide carrying esterified carboxyl groups, and a substance which performs a transacylation reaction with said polysaccharide, selected from the group consisting of a polyamine and a polyhydroxylic substance;
• b) providing a hydrophobic liquid in which the esterified polysaccharide and the polyamine are essentially insoluble;
• c) mixing the hydrophobic liquid and the aqueous solution to form an emulsion;
• d) adding a solution of an alkaline substance in an organic liquid miscible with the aqueous phase to the hydrophobic liquid provided under b) or to the emulsion formed under c);
• and
• e) maintaining the contacting of said solution of alkaline substance in said organic liquid with said hydrophobic liquid for a period of time sufficient to form said microparticles.

A process for the manufacture of microparticles, which comprises the following successive steps:

• (a) preparing a substantially neutral aqueous solution of a polysaccharide carrying esterified carboxyl groups;
• (b) preparing a hydrophobic solution of a substance capable of reacting with said polysaccharide selected from the group consisting of a polyamine substance and a polyhydroxylic substance, in a hydrophobic liquid in which the esterified polysaccharide is essentially insoluble;
• (c) preparing a solution of an alkaline agent in an organic liquid miscible with the aqueous phase;
• (d) mixing the solution of the alkaline agent in the organic liquid miscible with the aqueous phase with said hydrophobic solution prepared under (b), thereby getting a hydrophobic phase;
• (e) forming an emulsion of the hydrophobic phase as the dispersed phase in the neutral aqueous solution of the esterified polysaccharide as the continuous phase and allowing a transacylation reaction to develop on the surface of the dispersed droplets of said hydrophobic phase by diffusion of the alkaline ions to the interface during a period of time sufficient to form said microparticles;
• and
• (f) adding to said emulsion a solution of an acid substance in a solvent selected from the group consisting of an organic liquid miscible with the aqueous phase and water thereby neutralizing and stabilizing said microparticles.

A substantially process for the manufacture of microparticles comprising the following successive steps:

• (a) preparing a neutral aqueous solution of polysaccharide carrying esterified carboxyl groups;
• (b) preparing a solution of a core acting substance capable of reacting with said polysaccharide, selected from the group consisting of a polyamine substance and a polyhydroxylic substance, in a hydrophobic liquid in which the esterified polysaccharide is essentially insoluble;
• (c) forming an emulsion of the aqueous solution as the disperse phase in the hydrophobic liquid as the continuous phase;
• (d) adding to the emulsion a solution of an alkaline substance in an organic liquid miscible with the aqueous phase to initiate an interfacial transacylation reaction which is performed during a period to time sufficient to form said microparticles;
• and
• (e) adding to the emulsion a solution of an acid substance in an organic liquid miscible with the aqueous phase to neutralize and stabilize the microparticles.