齐墩果酸纳米粒的制备及质量控制

目的:制备齐墩果酸(OA)纳米粒并建立其质量控制方法。方法:以OA为主药,乳酸羟基乙酸共聚物(PLGA)为载体材料,采用超声乳化-溶剂挥发法制备纳米粒;取投料比、超声强度、超声时间、磁力搅拌时间为因素,包封率、平均粒径、载药量为指标设计正交试验筛选处方;利用反相高效液相色谱(RP-HPLC)法测定制剂中主药的含量,同时以磷酸盐缓冲液为介质、采用透析袋法进行体外释放度考察。结果:最佳处方为OA与PLGA投料比2∶5,超声功率400W,超声时间12min,磁力搅拌48h;所制纳米粒呈球形,平均粒径324.6nm,Zeta电位(-4.76±0.373)mV,载药量为(27.26±2.41)%,包封率为(91.82±3.19)%;OA检测浓度的线性范围为5～80μg·mL-1(r=0.9986),平均回收率为100.06%,平均日内RSD为2.43%、日间RSD为2.93%;药物前12d呈快速释放,12d后呈缓慢恒速释放。结论:该制剂制备方法简单,质量稳定可控。

Preparation and Quality Control of Oleanolic Acid-loaded Nanoparticles

OBJECTIVE： To prepare Oleanolic acid （OA）-loaded nanoparticles （NP） and to establish its quality control method. METHODS： NP was prepared using OA as main component and polylactic-co-glycolic acid （PLGA） as carrier by ultrasonic emulsification-solvent evaporation technique. Formulation was optimized with drug dosage ratio, intensity and time of ultrasonic and time of magnetic force stirring as factors and encapsulation efficiency, mean particle size and drug-loading amount as index. The content of OA was determined by RP-HPLC and in vitro drug release of OA-loaded nanoparticles was determined by dialysis bag using phosphate buffer as medium. RESULTS： Optimized formulation of NP was as follows： ratio of OA to PLGA was 2 ∶ 5, ultrasonic power 400 W, ultrasonic time 12 min, magnetic force stirring for 48 h. NPs were sphere-like with mean diameter of 324.6 nm, drug-loading amount of （27.26±2.41）%, Zeta potential of （-4.76±0.373） mV and encapsulation efficiency of （91.82±3.19）%. The linear range of OA was 5～80 μg·mL^-1 （r=0.998 6） with an average recovery of 100.06%. The RSD of intra-day and inter-day were 2.43% and 2.93%. NP released rapidly at the first 12 days while slowly and stably after 12 days. CONCLUSION： The method is simple, stable and controllable in quality.