羟丙甲基纤维素作为过饱和自乳化给药系统的沉淀抑制剂的机制研究  

Mechanisms of hydroxypropyl methylcellulose for the precipitation inhibitor of supersaturatable self-emulsifying drug delivery systems

作　　者：肖璐[1] 易涛[1] 

机构地区：[1]澳门科技大学,澳门药物及健康应用研究所,中药质量研究国家重点实验室,中国澳门000853

出　　处：《药学学报》2013年第5期767-772,共6页Acta Pharmaceutica Sinica

基　　金：澳门科学技术发展基金项目(094/2012/A3)

摘　　要：羟丙甲基纤维素可促使自乳化给药系统(SEDDS)在胃肠道形成过饱和状态,对增强水难溶性药物吸收具有重要意义。本文在体外模拟胃肠道环境中研究了不同黏度的羟丙甲基纤维素[HPMC(K4M、K15M、K100M)]对SEDDS药物沉淀的抑制作用及其机制。结果显示:HPMC通过抑制晶核形成和晶体生长而抑制SEDDS在胃分散后的药物沉淀;HPMC对SEDDS的脂解速率有明显影响,而且有利于SEDDS脂解后药物分配进入水性分散相并抑制药物沉淀,其机制与HPMC黏度、分子质量以及形成的网络空间结构有关。这些研究结果为选择合适类型的HPMC作为过饱和SEDDS的沉淀抑制剂提供了参考依据。Hydroxypropyl methylcellulose （HPMC） propels self-emulsifying drug delivery systems （SEDDS） to achieve the supersaturated state in gastrointestinal tract, which possesses important significance to enhance oral absorption for poorly water-soluble drugs. This study investigated capacities and mechanisms of HPMC with different viscosities （K4M, K15M and K100M） to inhibit drug precipitation of SEDDS in the simulated gastrointestinal tract environment in vitro. The results showed that HPMC inhibited drug precipitation during the dispersion of SEDDS under gastric conditions by inhibiting the formation of crystal nucleus and the growth of crystals. HPMC had evident effects on the rate of SEDDS lipolysis and benefited the distribution of drug molecules across into the aqueous phase and the decrease of drug sediment. The mechanisms were related to the formed network of HPMC and its viscosities and molecular weight. These results offered a reference for selecting appropriate type of HPMC as the precipitation inhibitor of supersaturatable SEDDS.

关 键 词：自乳化给药系统 羟丙甲基纤维素 过饱和 沉淀抑制剂 体外脂解 

分 类 号：R943[医药卫生—药剂学]