高水溶性药物在微球制备工艺中关键工艺的优化  

Key Process Optimization in Preparation of Microspheres Loaded with Highly Water-soluble Drugs

作　　者：陈卫 刘吉伟 李学明[2] CHEN Wei;LIU Jiwei;LI Xueming(Nanjing Bestform Pharmtech Co.,Ltd.,Nanjing 210000;Nanjing Tech University,Nanjing 211816)

机构地区：[1]南京百思福医药科技有限公司,江苏南京210000 [2]南京工业大学,江苏南京211816

出　　处：《中国医药工业杂志》2021年第5期669-676,共8页Chinese Journal of Pharmaceuticals

基　　金：江苏省高等学校自然科学研究(18KJB350003)。

摘　　要：以醋酸奥曲肽为模型多肽制备聚乳酸-羟基乙酸共聚物(PLGA)微球,通过对关键工艺的优化,解决高水溶性药物在微球制备过程中包封率低,且长期释药过程中多肽药物与PLGA发生酰化副反应的问题。先将离子对试剂葡聚糖硫酸钠(DSS)与醋酸奥曲肽制成可逆性复合物,再联合添加磷酸钙以抑制PLGA与多肽药物发生酰化副反应的策略,采用s/o/w型复乳化-溶剂挥发法制备了醋酸奥曲肽微球。结果显示,与不含磷酸钙及离子对试剂DSS的载药微球相比,本工艺制品的酰化副反应率从15.12%下降到6.73%,包封率从44.85%增至92.18%。本研究通过关键工艺的优化,全面改善了PLGA微球中高水溶性多肽药物的包封和递送,为解决该类问题提供了新的思路和方法。To solve the problems of low encapsulation of highly water-soluble drugs in microspheres and acylation reaction between peptides and poly(lactic-co-glycolic acid)(PLGA)during the long-term drug release,the key process of PLGA microspheres loaded with octreotide acetate as a model peptide was investigated and optimized.Firstly,the ion-pairing reagent dextran sodium sulfate(DSS)was added to form reversible complexes.Then,calcium phosphate was added to inhibit the acylation side reaction between peptides and PLGA.The final microspheres were obtained by solid-in-oil-in-water double emulsion-solvent evaporation method.Compared with the octreotide acetate microspheres without DSS and calcium phosphate,the occurrence rate of acylation reaction of the final microspheres decreased from 15.12%to 6.73%,and the encapsulation efficiency increased from 44.85%to 92.18%.Due to the advantages of our design,the composite strategy comprehensively improved the issues of encapsulation and delivery of water-soluble peptide drugs in PLGA microspheres.This study provides a new perspective to improve the disadvantages of peptide delivery in PLGA microspheres.

关 键 词：醋酸奥曲肽 微球 聚乳酸-羟基乙酸共聚物 包封率 酰化副反应 

分 类 号：R944.9[医药卫生—药剂学]