Box-Behnken设计-响应面法优化西洋参茎叶皂苷口服脂质体处方

Box-Behnken design-response surface methodology to optimize the formulation of Panax quinquefolium saponins liposome for oral use

目的筛选出薄膜分散法制备西洋参茎叶皂苷脂质体(Panax quinquefolium saponins liposome,PQS-Lip)的最佳处方。方法在单因素试验的基础上,考察胆固醇琥珀酸单酯(cholesteryl hemisuccinate,CHEMS)的质量、氢化大豆卵磷脂(hydrogenated soya phosphatidylcholine,HSPC)的质量和脱氧胆酸钠(sodium deoxycholate,SDC)的质量对脂质体包封率的影响,采用Box-Behnken设计实验对薄膜分散法制备西洋参茎叶皂苷脂质体处方工艺进行优化,并利用响应曲面法进行分析,最后对其形态、粒径和体外释放行为进行评价。结果最佳工艺条件为:m(CHEMS)为166.98 mg,m(HSPC)为0 mg,m(SDC)为0 mg,理论包封率为73.67%,在此条件下的实际平均包封率为72.87%,接近理论预测值,说明该方法具有较好的预测性。结论 Box-Behnken设计结合响应曲面分析法有效地优化了西洋参茎叶皂苷口服脂质体的处方工艺,所制备的脂质体包封率高,粒度均匀,缓释效果明显,且工艺简单,适合工业生产。

Objective To screen the optimized formulation of Panax quinquefolium saponins liposome(PQS-Lip)by thin-film dispersion method.Methods Based on the single-factor experiment,the influence of mass of cholesteryl hemisuccinate,mass of hy-drogenated soya phosphatidylcholine and mass of sodium deoxycholate on the entrapment efficiency were studied.The Box-Behnken design experiment was used to optimize the formulation of PQS-Lip prepared by thin-film dispersion method,and the response surface methodology was used for analysis.Finally,the morphology,particle size and release profile in vitro were evaluated.Results The optimal formulation was as follow:the mass of CHEMS was 166.98 mg,the mass of HSPC and SDC was 0 mg.The theoretical entrapment efficiency was 73.67%,and the actual average entrapment efficiency was 72.87% under this condition,which was close to the theoretical prediction value,indicating that the method had good predictability.Conclusion Box-Behnken design-response surface methodology optimizes the formulation of Panax quinquefolium saponins liposome for oral use effectively,and the prepared liposome has high entrapment efficiency,uniform particle size,and significant sustained release effect.Besides,the procedure is simple and suitable for the industrial production.