联苯双酯过饱和自微乳释药系统的体内外评价

 目的 研究联苯双酯过饱和自微乳(BDD-S-SMEDDS的体外自乳化能力和体内药动学。方法 采用动态光散射法测定BDD-S-SMEDDS乳化后的粒径分布和Zeta电位；考察不同的促过饱和物质及不同用量对BDD-S-SMEDDS体外析晶的影响，并测定BDD-S-SMEDDS的体外溶出度；测定Beagle犬体内血药浓度，与市售滴丸相比，考察BDD-S-SMEDDS的体内药动学。结果 聚乙烯吡咯烷酮K30（PVP的促过饱和效果较好，其用量为0.5％～2％时均有较好的药物抑晶作用；BDD-S-SMEDDS加入水稀释后迅速乳化形成微乳，平均粒径为(38.40±0.28 nm，Zeta电位为(-8.00±0.99 mV；体外溶出度10 min时达到80％以上，比市售滴丸溶出显著提高；体内药动学数据表明，BDD-S-SMEDDS软胶囊达峰时间t_max提前，最大血药浓度ρ_max(143.29±52.91 μg·L-1是市售滴丸的2.6倍，AUC为市售滴丸的1.92倍。结论 BDD-S-SMEDDS体系中促过饱和物质PVPK30的加入，可以提高稳定性，减少表面活性剂的用量，并且显著提高BDD的体外溶出和体内吸收。

Assessment of a Supersaturated Self-Microemulsifying Formulation of Biphenyl Dimethyl Dicarboxylate in Vitro and in Vivo

OBJECTIVE To develop and characterize supersaturated self-microemulsifying drug delivery systems(S-SMEDDS) of biphenyl dimethyl dicarboxylate(BDD) and to evaluate the self-emulsification capability in vitro and the bioavailability in beagle dogs.METHODS The self-emulsification properties,particle size and Zeta potential of different formulations upon addition to water under mild stirring were studied.Supersaturated additives were selected as crystallization inhibitor,and the accumulated dissolution of the f...