多烯紫杉醇纳米乳的研制和质量评价

Preparation and Evaluation of Docetaxel Nanoemulsion

目的研制多烯紫杉醇纳米乳并对其质量进行评价。方法先测定多烯紫杉醇在不同油相中的溶解度,再采用伪三元相图法研究不同乳化剂、助乳化剂和Km值形成纳米乳的能力和区域,绘制不同处方组成的相图,在此基础上制备多烯紫杉醇纳米乳;并对纳米乳的物理性质、稳定性进行研究。结果以辛癸酸甘油三酯/聚氧乙烯氢化蓖麻油/聚乙二醇400/水形成了均匀稳定,粒径呈正态分布的纳米乳系统;用不同的介质稀释后,多烯紫杉醇纳米乳的粒径变化差异不明显;初步稳定性实验表明,多烯紫杉醇纳米乳在强光和高温条件下放置10d,室温储存3个月,药物含量和粒径均没有显著变化,稳定性良好。结论多烯紫杉醇纳米乳制备简单,质量稳定,为开发多烯紫杉醇新型口服制剂提供了依据。

OBJECTIVE To study the preparation of docetaxel nanoemulsion and its quality evaluation. METHODS Doeetaxel nanoemulsion was prepared by using the titration methods to obtain the pseudo-ternary diagram. The effect of various elements on the formation of the nanoemulsion was investigated. Physico-chemical property and stability of docetaxel nanoemulsion were evaluated. The contents of docetaxel in nanoemulsion were determined by HPLC method and the droplet size of docetaxel nanoemulsion were determined by a laser particle analyzer. RESULTS Docetaxel nanoemulsion prepared with RH-40 and PEG 400 at the ratio of 2.5： 1, and 35% of MCT, was uniform and stable colloidal system. The droplet size of docetaxel nanoemulsion was within 100 nm and showed Gaussian distribution, and kept constant all in distilled water, HCl and PBS solution. The preliminary stability test showed that the drug content and droplet size of docetaxel nanoemulsion were stable at high temperature and 4 500 lx condition for 10 d and at ambient temperature for 3 months. CONCLUSION The docetaxel nanoemulsion is easy to prepare by using MCT/RH-40/PEG-400/water and its quality is stable. A new form of delivery system for docetaxel was developed.