The invention belongs to the technical field of
crystal compound preparation, and particularly relates to a
crystallization process of small-particle-size
palmitic acid paliperidone. The invention discloses a small-particle-size
palmitic acid paliperidone crystallization process, solves the problems of
large particle size, non-uniform distribution and serious agglomeration of the existing process product, and meets the requirements of long-acting injection bulk drugs. The process comprises the following steps: adding
paliperidone palmitate into a specific mixed
organic solvent according to a
solid-to-
liquid ratio of 0.04-0.09 g / g, stirring, dissolving and filtering at 65-75 DEG C, transferring into a high-pressure closed crystallizer, and pressurizing to 1.0-1.5 MPa; cooling and decompressing in sections, stirring, filtering and washing, and
drying in vacuum at the temperature of 40-50 DEG C and the vacuum degree of-0.1 MPa to obtain a finished product. According to the invention, the process parameters are accurately controlled, the product is an irregular short rod-like / granular
crystal, the particle size is in a normal single peak, the Dv (90) is 7.866-9.514 microns, the HPLC (
High Performance Liquid Chromatography) purity is greater than or equal to 99.92%, the yield is greater than or equal to 90.25%,
micronization is not needed, the process is stable, the economical efficiency is good, and the industrial application value is realized.