卡巴他赛纳米混悬剂的制备与质量评价

Preparation and Quality Evaluation of Cabazitaxel Nanosuspension

目的:制备卡巴他赛纳米混悬剂,并考察其理化性质。方法:采用高压均质法制备卡巴他赛纳米混悬剂,以粒径分布作为评价指标,均质压力(X_1)和均质次数(X_2)为考察对象,利用Box-Behnken效应面法优化卡巴他赛纳米混悬剂的制备工艺;考察卡巴他赛纳米混悬剂的外观、微观形态、平均粒径、Zeta电位等理化性质,比较卡巴他赛纳米混悬剂与市售卡巴他赛注射液的体外释药行为。结果:卡巴他赛纳米混悬剂最优制备工艺为:850 bar均质压力下均质处理6次,制备的卡巴他赛纳米混悬剂在扫描电镜下呈大小均匀分布,平均粒径为(208.6±33.6)nm,PdI为(0.179±0.015),Zeta电位为(-32.4±0.3)mV,将卡巴他赛制备成纳米混悬剂可提高其体外溶出速率。结论:高压均质法制备卡巴他赛纳米混悬剂工艺简单易行,卡巴他赛纳米混悬剂能够加快药物释放,提高药物体外溶出速度。

Objective： To prepare cabazitaxel nanosuspension and investigate the physical and chemical properties. Methods：Cabazitaxel nanosuspension was prepared by a high pressure homogenization method. The homogeneous pressure（ X_1） and homogeneous number（ X_2） were used as the investigation objects,the particle size distribution was used as the evaluation index,and Box-Behnken response surface methodology was used to optimize the preparation process of cabazitaxel nanosuspension. The appearance,microstructure,particle size distribution and zeta potential of cabazitaxel nanosuspension were investigated. The drug release characteristics of cabazitaxel nanosuspension in vitro were compared between cabazitaxel nanosuspension and cabazitaxel injection. Results： The optimum preparation process of cabazitaxel nanosuspension was as follows： the homogenization pressure was 850 bar and the homogenization number was 6 times. The average particle size of the prepared cabazitaxel nanosuspension was（ 208. 6 ± 33. 6） nm,the PdI was（ 0. 179 ± 0. 015） and the zeta potential was（-32. 4 ± 0. 3） mV. Scanning electron microscopy showed that the size distribution of cabazitaxel nanosuspension was uniform. The in vitro dissolution rate of cabazitaxel nanosuspension was significantly higher than that of cabazitaxel injection. Conclusion： The preparation of cabazitaxel nanosuspension by the high pressure homogenization method is simple and feasible. Cabazitaxel nanosuspension can accelerate the drug release and increase the dissolution rate of drug in vitro.