星点设计-效应面法优化普萘洛尔传递体的处方工艺

Study on the Optimal Formulation and Preparation Conditions of Propranolol-loaded Transfersomes by Central Composite Design and Response Surface Method

目的应用星点设计-效应面法优化普萘洛尔传递体的处方工艺。方法采用硫酸铵梯度法制备普萘洛尔传递体。将药物/磷脂摩尔比、Span-80/磷脂摩尔比、探头超声时间作为考察因素,以包封率、载药量、平均粒径及变形性指数为效应指标,求算总评"归一值"并采用Design-Expert 8.0软件进行效应面法优化,确定最佳处方工艺并进行验证。结果确定最优制备工艺为:药物/磷脂摩尔比19.83%、Span-80/磷脂摩尔比21.08%、探头超声时间10.29 min,以该处方工艺制备所得传递体的包封率、载药量、平均粒径及变形性指数分别为76.63%,4.80%,52.82 nm,20.83,且实测值与预测值的偏差均较小。结论星点设计-效应面法适用于普萘洛尔传递体的处方工艺优化,优化所得处方工艺稳定、可行。

OBJECTIVE To optimize the formulation and preparation of propranolol-loaded transfersomes by central composite design and response surface method. METHODS Transfersomes were prepared using the ammonium sulfate gradient method. The effects of drug/lipoid molar ratio, Span-80 molar ratio and time of probe ultrasonication on entrapment efficiency, drug-loading, vesicle size and deformability index were investigated. After each overall desirability was calculated, the optimal conditions for preparing propranolol transfersomes were achieved by Design-Expert 8.0 software, and were validated experimentally. RESULTS The optimal preparation conditions were determined as drug molar ratio 19.83%, Span-80/lipoid molar ratio 21.08%, time of probe ultrasonication 10.29 min. Under these conditions, the evaluated entrapment efficiency, drug-loading, vesicle size and deformability index of propranolol transfersomes were 76.63%, 4.80%, 152.82 nm, 20.83 respectively, and all approximated to the forecasted ones. CONCLUSION The central composite design and response surface method is applicable for the formulation and preparation conditions of optimization of propranolol transfersomes, and the resulting optimal preparation technique is stable and feasible.