基于QbD理念研究醋酸奥曲肽PLGA微球的冻干工艺  

Study on Freeze-drying Process of Octreotide Acetate PLGA Microspheres Based on Quality by Design

作　　者：高飞[1] 安广峰 鲍菲[1] 刘万卉[1] 

机构地区：[1]烟台大学药学院,山东烟台264005 [2]山东绿叶制药有限公司,山东烟台264003

出　　处：《食品与药品》2017年第1期7-12,共6页Food and Drug

摘　　要：目的研究醋酸奥曲肽乳酸-羟基乙酸共聚物(PLGA)微球的冻干工艺,建立合适的冻干工艺参数控制区间。方法基于质量源于设计(QbD)理念,采用JMP10.0.0软件设计并执行试验,分析冻干工艺参数对样品质量属性的影响。结果第一阶段干燥参数板温、冻干时间和真空度对样品的有关物质无影响,板温和冻干时间对样品的水分和二氯甲烷残留有显著影响。第二阶段干燥参数板温对样品的有关物质有显著影响;冻干时间对样品的水分有显著影响;板温和冻干时间对样品的二氯甲烷残留有显著影响。结论采用冻干法干燥醋酸奥曲肽PLGA微球时,最终控制冻干全过程干燥参数设计区间为:预冻阶段控制板温≤-20℃,预冻时间≥3 h,真空度为常压;第一阶段干燥控制板温-5℃,冻干真空度≤5 Pa,冻干时间>2 h;第二阶段干燥控制板温45~50℃,冻干真空度≤5 Pa,冻干时间>14 h。Objective To study the freeze-drying process of octreotide acetate PLGA microspheres and establish suitable parameter design space of freeze-drying process. Methods The experiments design was carried out on the basis of QbD concept, and the influence of freeze-drying process parameters on the sample quality properties were analyzed by the experiments designed with software JMP10.0.0. Results The larst-stage arylng parameters SUCh as plate temperature, freeze-drying time and vacuum degree had no significant effects on the related substances; the plate temperature and freeze-drying time had significant effects on the moisture and methylene chloride residue. The plate temperature of the second-stage drying process had a significant effect on the related substances of the samples. The freeze-drying time had a significant effect on the moisture content. The plate temperature and freeze-drying time had significant effects on the methylene chloride content of the samples. Conclusion The freeze-drying process design space of the microspheres was summarized as follows： pre-freezing step, plate temperature no more than -20℃, pre- freezing time no less than 3 h and atmospheric pressure; first drying step, plate temperature of -5 ℃, vacuum degree no more than 5 Pa and freeze-drying time no less than 2 h; second drying step, plate temperature 45-50℃, vacuum degree no more than 5 Pa and freeze-drying time no less than 14 h.

关 键 词：醋酸奥曲肽 乳酸-羟基乙酸共聚物缓释微球 冻干 质量源于设计 设计空间 

分 类 号：R943[医药卫生—药剂学]