伊维菌素聚乳酸微球制备条件的优化及药物含量测定

OPTIMIZATION OF MICROSPHERE PREPARATION PROCEDURE AND HPLC DETERMINATION OF IVERMECTIN CONTENT IN THE POLY ( dl- LACTIC ACID) MICROSPHERES

用乳化溶剂挥发法制备了伊维菌素（ＩＶＭ）聚乳酸（ＰＬＡ）微球试验采用Ｌ１８（３７）正交设计，以微球粒径分布为主要优选水平，结合微球收率和包裹率，筛选出最佳制备条件：连续相为２０ｇ·Ｌ－１的聚乙烯醇（ＰＶＡ）水溶液；分散相为ＰＬＡ（Ｍｒ８２万，投量２０ｇ）和ＩＶＭ原料药（０６７或１００ｇ）溶于２５ｍＬ二氯甲烷；搅拌速度为４５０ｒ·ｍｉｎ－１，在３７℃恒温下搅拌１２ｈ挥干二氯甲烷，过滤收集微球所得微球干燥后呈白色粉末状，微球平均收率为８７９０％±１１６％［ｗ（ＩＶＭ）理论值为２５０％］和８８．３３％±２．６８％［ｗ（ＩＶＭ）理论值为３３．３％］采用溶解沉淀法，以ＲＰ－ＨＰＬＣ－ＵＶ法测定微球中药物含量：以二氯甲烷和甲醇（１∶９）为溶媒，可完全沉淀聚合物；药峰分离完全，无干扰峰；

Poly( d l -lactic acid)(PLA) microspheres(MS) containing ivermectin(IVM) were prepared by an oil in water solvent evaporation method. By using L 18 (3 7) orthogonal design and taking size distribution as main optimization factor,the best prescription and method were selected. The critical controlling variables of particle size were PLA and IVM concentration in organic phase,polyvinyl alcohol(PVA) concentration in continuous phase and the stirring speed for mixing of the two phases. The optimal experimental conditions to produce spherical and discrete drug loaded microspheres were as follows: the dispersed phase was PLA(2 0 g) and IVM(0 67 and 1 00 g) dissolved in methylene chloride; the continuous phase was 20 g·L -1 PVA; polymer drug solution was mixed into emulsifier solution by stirring at a speed of 450 r·min -1 to form a dispersion. An HPLC method with UV detection was established for determining the ivermectin content in the PLA microspheres. By dissolving 20 mg MS in methylene chloride (1 mL) and precipitating with methanol(9 mL),the IVM content in the microspheres was determined by RP HPLC UV method. This assay was simple,practicable and reproducible. The recovery rate was up to 95 85%±0 84%. The encapsulation efficiency were 97.90%±2.41% and 95.13%±4.66%,respectively, for IVM loaded PLA microspheres with theoretical IVM mass fraction of 25.0 % and 33.3%. Stored at room temperature for 30,60 and 90 days,the determined IVM contents in MS with theoretical IVM mass fraction of 25% and 33.3% were not different from those of newly prepared ones.