人参稀有皂苷Compound K混合胶束的处方优化及体外评价

Formulation Optimization and in vitro Evaluation of Rare Ginsenoside Compound K Mixed Micelles

目的:优化人参稀有皂苷Compound K(CK)混合胶束的处方,考察其体外释放度和表观渗透系数(Papp)。方法:以大豆磷脂和维生素E聚乙二醇1000琥珀酸酯(TPGS)为辅料,采用溶剂挥发法制备CK混合胶束。以载药量、包封率、粒径为指标,采用正交试验优化投药量、大豆磷脂-TPGS比例、水化体积。考察最优处方所制胶束的形态、粒径、载药量、包封率、溶解度、体外释放度和在结肠腺癌Caco-2细胞模型中的Papp。结果:CK混合胶束的最优处方投药量为1.0 mg,大豆磷脂-TPGS比例为1∶1,水化体积为10 ml。所制混合胶束呈球形或类球形,平均粒径为(110±2.69)nm,载药量为(4.32±0.19)%,包封率为(92.23±2.76)%,溶解度为(469.21±0.024)μg/ml,150 h时累积释放度为(66.19±0.027)%(n=3)。CK原料药和CK混合胶束的Papp分别为26.20、3.78(n=6)。结论:优化的制备工艺可行,成功制得CK混合胶束。

OBJECTIVE： To optimize the formulation of rare ginsenoside Compound K （CK） mixed micelle, and to investi- gate its in vitro release and apparent permeability coefficients （Papp）. METHODS： Using soy lecithin and vitamin E polyethylene glycol 1 000 succinate （TPGS） as excipients, CK mixed micelle was prepared by solvent evaporation method. Using drug-loading amount, encapsulation efficiency and particle size as index, orthogonal test was adopted to optimize feeding amount, the ratio of granulesten to TPGS and hydration volume; the micelle prepared by optimal formulation was investigated in respects of form, particle size, drug-loading amount, encapsulation efficiency, solubility, in vitro release; Papp of colon adenocarcinoma Caco-2 cell model was also inspected. RESULTS ： The optimal formulation was as follows as feeding amount 1.0 mg, the ratio of granulesten to TP- GS 1 ： 1, hydration volume 10 ml. The mixed micelles were spherical or spheroidal; the average particle size was （110 ± 2.69） nm, and drug-loading amount was （4.32 ±0.19）%, entrapment efficiency was （92.23 ± 2.76）%, and average solubility was （469.21± 0.024） μg/ml; 150 h accumulative release rate was （66.19 ±0.027）% （n=3）. Papp of CK crude drug and CK mixed micelle were 26.20 and 3.78 （n=6）. CONCLUSIONS： The optimized preparation technology is feasible, and CK mixed micelle is prepared successfully.