注射用利培酮微球的制备和体外性质评价

Preparation and in vitro evaluation of risperidone loaded PLGA microspheres

目的:制备注射用利培酮微球并进行质量评价。方法:建立HPLC方法测定利培酮的含量;以乳酸-羟基乙酸共聚物(PLGA)为载体材料,乳化-溶剂挥发法制备利培酮微球,考察药物量、载体量、乳化和固化聚乙烯醇(PVA)浓度对利培酮微球药剂学性质的影响,并对所制备的利培酮微球进行了体外释放度评价。结果:建立了利培酮含量测定的HPLC方法:采用Luna C18色谱柱,流动相为甲醇-水-三乙胺-冰醋酸(55∶45∶1∶0.5),流速为1 mL·min-1,检测波长为280 nm,柱温为25℃。根据不同因素对利培酮微球制备的影响,筛选出最佳处方:药物20 mg,载体400 mg,乳化PVA浓度为2%,固化PVA浓度为0.3%,所得的利培酮微球表面圆整,粒径为61.5μm,包封率为89.8%,载药量为6.8%。体外释放试验表明,按照最优处方制备的利培酮微球2 h内药物释放低于10%,突释效应较小;d 5药物的释放达到63%,可持续释放15 d。结论:本实验根据不同制备因素优化得到的利培酮微球,释放无滞后期,可有效缓释达两周以上。

Objective：To prepare risperidone loaded PLGA microspheres and evaluate its in vitro pharmaceutical characters. Methods：An HPLC method was established to determine the concentration of risperidone. Risperidone loaded poly （lactic-co-glycolide acid） （PLGA） microspheres were prepared by emulsion-solvent evaporation method. The effects of different preparation parameters on the preparation of risperidone microspheres were investigated, and the pharmaceutical characters of risperidone microspheres were evaluated. Results：The HPLC method was established. Luna C18 column was used with methanol-water-triethylamine-acetic acid（55：45： 1：0.5） as mobile phase. The flow rate was 1 mL. min-1, detecting wavelength was set at 280 nm, and column temperature was set at 25℃. The best formulation was obtained according to the effects of different factors on the preparation of risperidone microspheres. Spherical microspheres with a smooth surface and dispersive quality were prepared based on the best formulation. The particle size of risperidone microspheres was 61.5 μm. The encapsulation efficiency and the drug loading were 89.8% and 6.8% , respectively. The release of risperidone from microspheres in vitro was less than 10% in two hours and showed no burst release. The drug was released by 63% on the fifth day and could sustain for two weeks. Couclusion：Risperidone could release from PLGA microspheres constantly for two weeks,without lag phase. The prepared microspheres are helpful for improving patients＇ compliance and modifying clinical dosage.