紫杉醇纳米混悬剂的处方与工艺优化

Optimization of the formulation and process of Paclitaxel nanosuspension

目的研究紫杉醇纳米混悬剂的制备工艺与处方。方法采用超声沉淀法制备紫杉醇纳米混悬剂，以纳米粒的平均粒径、多分散系数（PDI）和Zeta电位为指标，采用单因素法来优化制备工艺和处方，并对最优工艺和处方所得制剂进行粒径和形态表征。结果紫杉醇纳米混悬剂的最佳制备工艺为：药物溶液注入速度60mL·min^-1，400W超声10min、重复2次，水相温度0℃；最佳处方为药物和稳定剂的质量比为1：1，即2mL无水乙醇，药物浓度为2mg·mL^-1；由粒径测定和透射电镜成像结果可知：紫杉醇纳米混悬剂具有小而均匀的粒径，且形态为矩形，不同于原料药的针状。结论所确定的最佳制备工艺和处方可满足紫杉醇纳米混悬剂的制备需要。

OBJECTIVE To optimize the prescription and process of paelitaxel nanosuspension. METHODS Paclitaxel nanosus- pensions （ PTX - Nanos） were prepared by ultrasonic precipitation. The average particle size, polydispersity coefficient （PDI） and Zeta potential of nanoparticles were used as indicators. Single factor method was employed to optimize the preparation process and formulation. The particle size and morphology of the nanosuspension manufactured by the optimal process and formulation were characterized. RESULTS The best preparation process of paclitaxel nanosuspension was worked out：the input rate of drug solution was 60 mL. min-l with ultrasonic power at 400 W, ultralsonic time for 10 min twice and temperature at 0 ℃. The best formulation was set as： Drug - stabilizer ratio of 1 ： 1,2 mL absolute ethanol and drug final concentration of 2 mg. mL -1. Aecording to the results of particle size assay and transmission electron microscopy,it was known that paclltaxel nanosuspension has a small and uniform particle size and was rectangular in shape, which different from the needle form of the raw paclitaxel. CONCLUSION The optimal process and prescription can meet the prepared needs of paclitaxel nanossuspensions and can be used in the subsequent study of paclitaxel nanossus- pensions.