目的 通过Box-Behnken试验设计(BBD)法优化人参皂苷Rg₃自乳化制剂的处方配比,并对其质量进行评价。方法 采用3因素3水平BBD,以乳化剂、助乳化剂和油相为主要因素进行考察,载药量和平均粒径为响应值,用BBD软件绘制响应面图并得到各考察因素对指标影响的多项式,最终得到优化的处方配比,通过对自乳化效率、粒径、溶出度等方面进行体外评价。结果 人参皂苷Rg₃自乳化制剂最优处方的乳化剂为[RH40-Triton X100(1:1)],助乳化剂为异丙醇,油相为油酸乙酯,最优比例为3:1.475:0.5;优化后制备的制剂5 min内乳化完全,平均载药量为917.53 μg/mL,平均粒径为111.6 nm,且体外溶出度试验表明其释药速度与程度明显优于市售的胶囊剂。结论 BBD法用于人参皂苷Rg₃自乳化制剂的处方优化是可行的,数学模型的预测值与实验观察值相符。

Objective To optimize the formulation of ginsenoside Rg₃ self-emulsifying drugdelivery by Box-Behnken experimental design (BBD) and evaluate its quality. Methods Formulations were optimized using design of experiments by employing a 3-factor, 3-level BBD. Independent variables studied were the emulsifier, co-emulsifier, and the oil phase. The dependent variables were drug loading and average particle size. Through the BBD software, the response surface plots were drawn and the polynomial of influence of each factor index was obtained. Finally the formula optimization was obtained and the efficiency, droplet size, and dissolution rate of self-emulsifying drug delivery were investigated. Results Optimum prescription was as follows: emulsifier [RH-400-Triton X-100 (1:1)], co-emulsifier (isopropanol), and the oil phase (ethyl oleate). The optimum proportion was 3:1.475:0.5. The optimized ginsenoside Rg₃ self-emulsifying drug delivery could fully emulsify in 5 min and the average drug loading was 917.53 μg/mL, average particle size was 111.6 nm. The dissolution degree in vitro of the formulations showed that the release rate and level were apparently superior to the conventional capsules. Conclusion The observed responses are in close agreement with the predicted values of the mathematic models, and the BBD is suitable for optimizing ginsenoside Rg₃ self-microemulsifying drug delivery.

浙江省中医药管理局课题(2011ZA075)