目的 制备高载药量、小粒径的槲皮素纳米混悬剂, 并进行性质考察。方法 采用纳米沉淀-高压均质法制备, 以粒径分布、药载比、稳定性为指标对处方和工艺进行优化, 并对最优处方进行体外性质考察。结果 以超声注入联合高压均质法制备, 最佳处方为TPGS为稳定剂、DMF为有机试剂, 药载比为5:1;最佳工艺条件为低温10 ℃超声、200 MPa、循环5次。制备得到的槲皮素纳米混悬剂粒径为(173.21±0.90) nm, 电位为(-19.02±0.15) mV, 载药量为(80.40±1.44)%, 包封率为(96.41±1.72)%。药物在纳米粒中以结晶状态存在, 能够体外缓释36 h。结论 利用TPGS可制备高载药量、小粒径的槲皮素纳米混悬剂, 其体外具有明显缓释作用, 解决了槲皮素水溶性差的难题, 具有较好的应用前景。

Objective To prepare Quercetin Nanosuspensions with high drug-loading capacity and small particle size, and study their behaviors in vitro. Methods Quercetin Nanosuspensions were prepared using nano-precipitation and high-pressure homogenization method. The formulation and preparation process were optimized using particle size distribution, drug loading capacity, and stability of samples as evaluating indicators, and then the properties in vitro of optimal sample were studied. Results Ultrasonic injection and high-pressure homogenization was selected as optimal method. The optimal prescription included using TPGS as the stabilizer with the drug-stabilizer ratio of 5:1, DMF as the organic reagent. The optimal preparation was as following: ultrasonic processing was under 10 ℃, the homogenization pressure was 200 MPa, and cycles were 5 times. The prepared Quercetin Nanosuspensions had average diameter (173.21 ± 0.90) nm and Zeta potential (-19.02 ± 0.15) mV. Drug-loading content was calculated to be (80.40±1.44) % and the entrapment efficiency was determined to be (96.41±1.72)%. Quercetin was in the same form of crystalline in Quercetin Nanosuspensions as in the bulk quercetin. Quercetin could release in a sustained release manner during 36 h. Conclusion Using the polymer TPGS, Quercetin Nanosuspensions with high drug-loading and small size sustained released are prepared, and it has obviously in vitro sustained released effect, which dissolves poor water solubility of quercetin, and has good prospect of application.

国家国际科技合作专项(2008DFA31070);黑龙江中医药大学重点实验室开放课题(2013kf04)