水飞蓟宾过饱和自微乳给药系统的制备及体外质量评价

Preparation and in vitro quality evaluation of silybin supersaturated self-microemulsion drug delivery system

目的开发和优化水飞蓟宾(SLB)过饱和自微乳给药系统(SLB-SSMEDDS),提高SLB在生物介质中的过饱和度以及延长过饱和时间。方法通过溶解度试验、乳化剂乳化能力的考察以及伪三元相图的绘制,筛选出SLB-SSMEDDS处方组成;采用层次分析法(AHP)综合评价各处方的性能以筛选最优处方比例;以维持药物在体外生物介质中的过饱和度和持续时间优选沉淀抑制剂(PPIs)的种类及其用量;从乳化效果、乳液大小及表面形貌,体外释药及体外过饱和度等角度全面评价SLB-SSMEDDS。结果 SLB-SSMEDDS处方为丙二醇单辛酸酯-聚氧乙烯氢化蓖麻油-二乙二醇单乙基醚-醋酸羟丙甲纤维素琥珀酸酯(10∶67.5∶22.5∶2),载药量为50.19 mg/g,形成的自微乳均一透明,乳滴呈大小均匀的圆球状分布,乳化时间为(30.67±4.16)s,平均粒径为(11.67±0.81)nm,多分散指数(PDI)为0.15±0.04,SLB-SSMEDDS在人工胃液和人工肠液2种生物介质中药物的溶出速率均显著升高,体外稀释过饱和度在120 min内可维持在10以上。结论 SLB-SSMEDDS制备工艺简单,能改善传统自微乳给药系统(SMEDDS)的稳定性问题,有效维持过饱和状态,增强SLB体外溶出。

Objective To develop and optimize the silybin supersaturated self-microemulsion drug delivery system(SLB-SSMEDDS)and improve the oral bioavailability of SLB in the biological medium.Methods The formulation of SLB-SMEDDS was selected by solubility test,emulsifying ability of emulsifier and pseudo-ternary phase diagram.The analytic hierarchy process(AHP)was used to evaluate the performance of each prescription to screen the optimal ratio.The type and dosage of precipitation inhibitors(PPIs)was optimized to maintain the supersaturation and duration of drugs in biological media in vitro;Finally,the emulsification effect,emulsion size and surface morphology of SLB-SSMEDDS was comprehensively evaluated in terms of in vitro release and in vitro supersaturation.Results The SLB-SSMEDDS prescription was Capryol 90-Cremophor RH-Transcutol HP-HPMC-AS MF(10∶67.5∶22.5∶2).The self-microemulsion with a drug loading of 50.19 mg/g was uniform and the emulsion droplets were spherical in shape and uniform in size.And the emulsification time was(30.67±4.16)s,the average particle size was(11.67±0.81)nm,and the PDI was(0.15±0.04).The dissolution rate of SLB-SSMEDDS in FaSSGF and FaSSIF-V2 was significantly increased.And the in vitro dilution and supersaturation could be maintained above 10 within 120 min.Conclusion SLB-SSMEDDS has a simple preparation process and can improve the stability of traditional SMEDDS,maintain supersaturation effectively and enhance the dissolution of SLB in vitro.