Preparation method of sustained-release microparticles

A method for preparing sustained-release microparticles comprising the following steps:

• 1) Preparing a solid dispersion of a water-soluble drug and a biodegradable and biocompatible poorly water-soluble polymer;
• the water-soluble drug is selected from the group consisting of goserelin, triptorelin, leuprorelin and octreotide;
• the biodegradable and biocompatible poorly water-soluble polymer is PLGA, wherein a ratio of the water-soluble drug to the PLGA is 1:1-99 by weight;
• 2) dissolving the solid dispersion prepared in step 1) in an organic solvent C to form a solid dispersion emulsion, the organic solvent C is dichloromethane;
• 3) adding the solid dispersion emulsion obtained in step 2) into a surfactant-containing aqueous solution to form a uniform emulsion;
• and
• 4) solidifying microparticles in the emulsion by solvent volatilization or solvent extraction, collecting the microparticles, washing with ultrapure water several times to remove the surfactant attached to the surface of the microparticles, and drying to obtain the sustained-release microparticles without trace of the organic solvent A and C, 100% of the water-soluble drug in the sustained-release microparticles is released in 60 days close to zero order release kinetics, wherein diameters of the microparticles are between 20 and 100 μm;
• wherein, step 1) is carried out by the following steps:
• 11) completely dissolving the biodegradable and biocompatible poorly water-soluble polymer and the water-soluble drug in an organic solvent A to form a mixed solution of the drug and the polymer;
• and
• 12) adding the mixed solution into an organic solvent B or adding the organic solution B into the mixed solution to produce a precipitate, collecting the precipitate, washing the precipitate with the organic solvent B several times, and removing the organic solvent B to obtain a solid dispersion of the water-soluble drug and the poorly water-soluble polymer, wherein the organic solvent B is incapable of dissolving the poorly water-soluble polymer and the water-soluble drug,
• organic solvent A is glacial acetic acid;
• and
• the organic solvent B is anhydrous diethyl ether.