Induced phase transition method for the production of microparticles containing hydrophilic active agents

A process for the production of polymeric microparticles comprising dissolving a polymer in a halogen-free solvent, said solvent being at least partially water-miscible, to form a polymer solution, said solvent being selected from acetone, ethanol, alkyl acetates, alkyl formates, triacetin, triethyl citrate, C1–C4-alkyl lactates, methyl ethyl ketone, methyl isobutyl ketone, tetrahydrofuran, dimethyl sulfoxide, 1-methyl-2-pyrrolidone, 3-methyl-1-butanol, acetonitrile, PEG 100, PEG 400, N-methyl-pyrrolidone, glycofurol, diethylcarbonate and 2-methyl-1-propanol and mixtures thereof;

• adding a hydrophilic active agent to the polymer solution to form a drug phase contained in a vessel;
• adding a predetermined amount of an aqueous surfactant phase, wherein the volume fraction of the surfactant phase is at least 0.60, to the vessel containing the drug phase with mixing, wherein δpolymer solvent−δaqueous phase<0, said predetermined amount being sufficient to provide that the surfactant phase becomes the continuous phase and extraction medium in order to extract an amount of said solvent from said drug phase such that a suspension of microparticles is produced upon addition of the surfactant phase to the drug phase without the formation of an intermediate W/O/W double emulsion and without requiring removal of solvent from the vessel, wherein a suspension of the polymeric microcapsules is formed within one minute of mixing the surfactant phase with the drug phase.