School of Pharmacy, Chongqing Medical University, Chongqing 400016, China.
Fitoterapia. 2012 Dec;83(8):1532-9. doi: 10.1016/j.fitote.2012.08.021. Epub 2012 Sep 6.
The main object of this work is to prepare self-microemulsifying drug delivery system (SMEDDS) for oral bioavailability enhancement of a poorly water-soluble drug, baicalein. SMEDDS is the mixture of surfactants, cosurfactants, and oils, which are emulsified in aqueous media under conditions of gentle agitation or gastrointestinal motility. Solubility of baicalein was determined in various vehicles. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region and droplet size distributions of the resultant microemulsions were determined using a particle size analyzer. Optimized SMEDDS formulations for baicalein were Cremophor RH40 (53.57%) as surfactant, Transcutol P (21.43%) as cosurfactant, and Caprylic capric triglyceride (ODO, 25%) as oil. The drug release rate of SMEDDS was significantly higher than that of the baicalein suspension. Comparison of the pharmacokinetics between baicalein-loaded SMEDDS and baicalein suspension was also performed in rats. The plasma concentrations of baicalein and baicalin, its mainly conjugated metabolite, were determined by HPLC method. The in vivo results showed that the absorption of baicalein from SMEDDS resulted in about 200.7% increase in relative bioavailability compared with that of the baicalein suspension. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as baicalein by the oral route.
这项工作的主要目的是制备自微乳给药系统（SMEDDS），以提高一种难溶性药物黄芩素的口服生物利用度。SMEDDS 是由表面活性剂、助表面活性剂和油混合而成，在温和搅拌或胃肠蠕动条件下在水介质中乳化。测定了黄芩素在各种载体中的溶解度。绘制了伪三元相图，以确定有效的自乳化区域，并使用粒径分析仪测定所得微乳液的粒径分布。黄芩素的优化 SMEDDS 配方为：表面活性剂为吐温 RH40（53.57%），助表面活性剂为 Transcutol P（21.43%），油为辛酸/癸酸三甘油酯（ODO，25%）。SMEDDS 的药物释放速率明显高于黄芩素混悬液。还在大鼠体内比较了黄芩素载药 SMEDDS 与黄芩素混悬液的药代动力学。采用 HPLC 法测定黄芩素及其主要结合代谢物黄芩苷的血浆浓度。体内结果表明，与黄芩素混悬液相比，SMEDDS 中黄芩素的吸收使相对生物利用度增加了约 200.7%。我们的研究表明，SMEDDS 可作为一种潜在的载体，通过口服途径递送疏水性化合物，如黄芩素。
