紫杉醇自微乳释药系统的制备及评价

Preparation and Quality Evaluation of Paclitaxel Self-Microemulsifying Drug Delivery System

目的研制紫杉醇自微乳并进行质量评价。方法考察紫杉醇在不同油相、乳化剂和助乳化剂中的溶解度,再通过滴制法绘制伪三元相图,确定最优的Km值和处方,制备紫杉醇自微乳;并考察自微乳的外观、形态、粒径、载药量和稳定性。结果以聚氧乙烯蓖麻油EL35-卵磷脂/无水乙醇/中碳链甘油酯/水形成了均匀稳定的系统;紫杉醇自微乳为淡黄色澄明液体,稳定,平均粒径19.4 nm,呈Gauss分布,透射电镜下成圆球形,分布均匀。自微乳经0.9%的氯化钠注射液和5%的葡萄糖注射液稀释10及50倍后,外观、pH值、载药量、粒径均无明显变化。结论紫杉醇自微乳易于制备、质量稳定,为紫杉醇新型制剂的研发提供了科学依据。

OBJECTIVE To prepare paclitaxel self-microemulsifying drug delivery system（PTX-SMEDDS） and evaluate its quality. METHODS The equilibrium solubility of paclitaxel in different compositions of oil, emulsifiers and assistant emulsifiers was in- vestigated. The optimal Km was determined and PTX-SMEDDS was prepared by using the method of titration to establish the pseudo-ter- nary phase diagram. The appearance, morphology, size distribution, concentration and stability of PTX-SMEDDS were determined. RE- SULTS PTX-SMEDDS prepared with EL-35, lecithin and anhydrous ethanol at the ratio of 4 ： 1 ： 6, containing 6% DOC-Na and 7.5% of MCT,was a uniform and stable colloidal system displaying as a translucent diluted-yellow solution. PTX-SMEDDS under elec- tron microscopy consisted of small spherical drops with a mean diameter of 19.4 nm. The appearance, pH, concentration and particle size of SMEDDS were stable after it was diluted with sodium chloride injection and glucose injection by 10-fold or 50-fold ,respectively. CONCLUSION The PTX-SMEDDS is easy to prepare and its quality is stable, which provieds some information for the development of new paclitaxel formulations.