目的采用Box-Behnken效应面法筛选最佳处方,制备盐酸小檗碱脂质体。方法采用薄膜分散-p H梯度法制备脂质体,分别以磷脂与胆固醇质量比、脂药质量比、外水相p H值、孵化温度为考察对象,以包封率、粒径和载药量为评价指标,采用4因素3水平Box-Behnken效应面设计法筛选盐酸小檗碱脂质体的最佳处方。采用阳离子交换树脂微柱离心法测定包封率,动态激光散射法测定脂质体的粒径,并采用透射电镜观察制得的脂质体形态。结果最优处方工艺条件为磷脂与胆固醇质量比为3.38∶1,脂药质量比为22∶1,外水相p H为6.88,孵化温度为59℃。以最优处方制备的盐酸小檗碱脂质体平均粒径、包封率、载药量与预测值偏差较小。结论采用Box-Behnken效应面法优化盐酸小檗碱脂质体工艺处方是可行的。 OBJECTIVE To select the best prescription with Box-Behnken effect surface method and prepare berberine hydrochloride liposomes. Methods Liposomes were prepared by thin-film dispersion-pH gradient method. The mass ratio of phospholipid to cholesterol, the mass ratio of lipid to lipid, the pH value of outer aqueous phase and the incubation temperature were used as the targets. The entrapment efficiency, particle size and drug loading Amount as the evaluation index, the optimal prescription of berberine hydrochloride liposomes was screened by Box-Behnken four-factor-three design method. The entrapment efficiency was determined by cation exchange resin micro column centrifugation. The size of liposomes was determined by dynamic laser light scattering. The morphology of liposomes was observed by transmission electron microscopy. Results The optimal prescription was as follows: mass ratio of phospholipid to cholesterol was 3.38:1, mass ratio of lipid to drug was 22:1, pH of external aqueous phase was 6.88 and incubation temperature was 59 ℃. The average particle size, encapsulation efficiency and drug loading of berberine hydrochloride prepared by optimal prescription were less deviation from the predicted value. Conclusion Box-Behnken effect surface method optimization berberine hydrochloride liposome process prescription is feasible.