醋酸奥曲肽微球的制备及工艺优化  

Preparation of octreotide acetate loaded poly(lactic-co-glycolic acid) microspheres and optimization of the formulation

作　　者：冷迪[1] 彭博[2] 王毅飞[2] 刘津爱 王明新[2] 王东凯[1] 

机构地区：[1]沈阳药科大学药学院 [2]中国医药研究开发中心有限公司

出　　处：《中国药剂学杂志（网络版）》2010年第1期1-8,共8页Chinese Journal of Pharmaceutics：Online Edition

摘　　要：目的使用星点设计-效应面法优化醋酸奥曲肽乳酸-羟基乙酸共聚物缓释微球的制备工艺,提高工艺优化结果的预测性。方法用复乳(W/O/W)-溶剂挥发法制备醋酸奥曲肽微球;以油相二氯甲烷体积及外水相聚乙烯醇、氯化钠质量分数为自变量,以微球平均粒径、跨距、载药量、包封率、产率及突释量为因变量,采用星点设计-效应面法优化工艺,并对优化后的工艺进行验证。结果成功制备了醋酸奥曲肽微球;优化得到的最佳工艺为二氯甲烷体积1.8mL,聚乙烯醇质量分数1.64%,氯化钠质量分数1.2%;按优化工艺制备的微球的平均粒径为51.74μm,跨距为1.58,载药量质量分数为5.50%,包封率质量分数为88.00%,产率质量分数为79.02%,突释质量分数为9.19%。结论星点设计-效应面法优化微球制备工艺预测性良好,所制备的微球具有较好的体外缓释特性。Objective To optimize the formulation of octreotide acetate loaded poly(lactic-co-glycolic acid) microspheres by central composite design-response surface methodology.Methods Double emulsion emulsification-solvent evaporation method was used to prepare octreotide acetate microspheres.The volume of CH2Cl2,polyvinyl alcohol(PVA) concentration and NaCl concentration in outer phase were listed as three independent variables and the dependent variables were mean diameter,span,drug content,encapsulation efficiency,yield and initial release.The central composite design-response surface methodology was constructed to optimize the formulations and the optimized formulation was validated.Results The optimized preparation conditions were as follows:the volume of CH2Cl2 1.8 mL,PVA mass concentration 1.63 %(m:m),NaCl mass concentration 1.2 %(m:m).According to these conditions,the mean diameter of the microspheres were 51.74 μm with span of 1.58.Drug content,encapsulation efficiency,yield and initial release of octreotide acetate microspheres were,5.50 %,88.00 %,79.02 % and 9.19 % respectively.The microspheres had obvious sustained release property.Conclusions Central composite design-response surface methodology is successfully used to optimize the preparation of octreotide acetate loaded sustained-release microspheres.

关 键 词：药剂学 微球 星点设计-效应面法 醋酸奥曲肽 乳酸-羟基乙酸共聚物 

分 类 号：R94[医药卫生—药剂学]