度他雄胺自微乳给药系统的制备和体外评价

Preparation and in vitro Evaluation of Dutasteride Self-microemulsions

通过溶解度和伪三元相图筛选度他雄胺自微乳给药系统(SMEDDS)的处方组成,并采用星点设计法,以粒径、电位及溶出度等为评价指标继续优化。所得优化空白处方为单辛酸甘油酯-聚氧乙烯35蓖麻油-1,2-丙二醇(1∶1.46∶1.46)。直接加入药物得到的载药SMEDDS在0.1 mol/L盐酸、pH 6.8磷酸盐缓冲液、pH 4.5乙酸盐缓冲液和水中的释放行为相似,与度他雄胺软胶囊(Avodart)相比,溶出情况明显改善。初步稳定性考察结果表明制品较稳定。

Based on the results of the solubility test and pseudo-ternary phase diagrams, the components of a blank self-microemulsifying drug delivery system （SMEDDS） were obtained. The formulation was further optimized by central composite design combined with response surface methodology with particle size, potential and in vitro dissolution of dutasteride as response variables. The optimal product was obtained by adding dutasteride into the blank SEMDDS consisting of caprylic monoglyceride, Cremophor EL and 1,2-propylene glycol with the weight ratio of 1 ; 1.46 ; 1.46. The dissolution behaviors of the product in four media （0.1 mol/L HC1, pH 6.8 phosphate buffer, pH 4.5 acetate buffer and water） were similar. Compared with the commercial dutasteride soft capsules （Avodart）, the dissolution of the SMEDDS was significantly improved. The results of the preliminary stability test showed that the product was rather stable.