基于QbD理念优化伊潘立酮微球的冻干工艺

Study on Freeze-drying Process of Iloperidone PLGA Microspheres Base on QbD

目的研究伊潘立酮聚乳酸-羟基乙酸共聚物(polylactic-co-glycolic acid,PLGA)微球的冻干工艺,优化工艺参数。方法以质量源于设计(QbD)理念进行工艺分析,使用JMP(11.2.0)软件进行实验设计及结果分析。结果样品水分的主要影响因素为一期干燥温度;样品二氯甲烷残留的影响因素为二期干燥温度及二期干燥真空度;样品有关物质的主要影响因素为二期干燥温度。结论预冻温度为-30℃,冻干时间为3 h,真空度为常压;一期干燥温度为-5℃,真空度为40 Pa,冻干时间为5 h;二期干燥温度为31~35℃,真空度为100Pa,冻干时间为10 h。

Objective To study the freeze-drying process and optimize the process parameters of iloperidone polylacticco-glycolic acid(PLGA)microspheres.Methods The freeze-drying process was analyzed by QbD.The experiments were designed and analyzed by JMP software(11.2.0).Results The main factors influencing the water content was the temperature of phase I.The solvent residue of the product was affected by the temperature and the vacuum of the phase II.The impurity of the sample was influenced by the temperature of the phase II.Conclusion The freeze-drying process of the microspheres was summarized as follows:in the pre-freezing step,the temperature was-30℃,and the pre-freezing time was not less than 3 h at atmospheric pressure;in drying phase I,the plate temperature was-5℃,the vacuum degree was 30-50 Pa and the freeze-drying time was not less than 5 h;in drying phase II,the plate temperature was 31-35℃,the vacuum degree was 100 Pa and freeze-drying time was not less than 10 h.