伊维菌素缓释微球注射液制备工艺研究

Study on the Preparation Technology of Ivermectin Sustained-release Microsphere for Injection

摘要:

以乳化溶剂挥发法制备伊维菌素(IVM)聚乳酸(PLA)微球，用该微球制备注射液并进行质量控制研究。采用Central Composite试验设计，对微球制备中的搅拌速度、投料比IVM:PLA、聚乙烯醇浓度3个因素进行响应面优化；采用L16(34)正交实验对助悬体系进行优化；制备IVM缓释微球注射液并进行质量评价。研究结果表明：优化后的搅拌速度为651 r/min,投料比为7:16，PVA浓度为1.47%，此条件下微球载药率为29.4%；优化后的助悬体系为微球粒径80μm，微球、吐温20与羟甲基纤维素钠含量分别为2.5%、1.5%、1%，在此条件下注射液沉降体积比为91.5%；经测定注射液的平均pH为7.2，体外20d内可以平稳释放，达到缓释效果，稳定性良好，这一研究过程为IVM缓释微球注射液的工业制备及在临床上安全应用奠定了一定基础。

Abstract:

Preparating the ivermectin(IVM) poly-lactic acid(PLA) microspheres by emulsified solvent evaporation method, and the research prepared the injection of the microspheres and established its quality control standards. Applying Central Composite to optimizing three factors which affect microspheres preparation including stirring speed, mass ratio of IVM:PLA and polyvinyl alcohol(PVA) concentration. The research used the orthogonal experiment to optimizing the suspension system, prepared the IVM microspheres injection and evaluated its quality control standards. The results suggests that the optimal microspheres preparation condition is 651r/min of stirring speed, 7:16 of the mass ratio and 1.47% of PVA, and under this condition the drug loading rate is 29.4%. The optimal suspension system is that the particle diameter is 80μm, and the contents of the microspheres, Tween 20 and sodium carboxymethyl cellulose are 2.5%, 1.5% and 1% respectively. The sedimentation volume ratio of the injection is 91.5%. Being evaluated the injection average pH is 7.2, and the effective component stably releases in 20 days in vitro which achieves sustained releasing effect. The preparation process lays the foundation the development of ivermectin sustained-release microsphere for injection and its safety application of the clinical usage.