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目的:为了增加难溶性药物索拉非尼(Sorafenib)的口服吸收,本研究制备索拉非尼自微乳化给药系统并测定其口服相对生物利用度。方法:以油酸乙酯(20%,w/w)为油相,聚山梨酯-80(48%,w/w)为主要乳化剂,聚乙二醇400(16%,w/w)和乙醇(16%,w/w)为助乳化剂制备索拉非尼自微乳化给药系统,以大鼠为实验动物测定其口服相对生物利用度。结果:自微乳化给药系统中索拉非尼的终浓度为20 mg.mL-1。该制剂乳化后粒径为20～25 nm,并可在去离子水,生理盐水及5%葡萄糖溶液中稳定存在8 h。与索拉非尼混悬液相比,自微乳化给药系统可以显著增加索拉非尼的血药浓度-时间曲线下面积(AUC0～72 h),峰浓度(Cmax)和平均滞留时间(MRT),降低清除率(CL)。尤其是与口服混悬液相比,其相对生物利用度提高约25倍。结论:索拉非尼自微乳化给药系统可以显著提高索拉非尼的口服吸收相对生物利用度,有望开发成为增加其口服吸收的药物制剂。
OBJECTIVE: To increase oral absorption of Sorafenib, a poorly soluble drug, this study was to prepare sorafenib self-microemulsifying drug delivery system and determine its relative oral bioavailability. Methods: Polysorbate-80 (48%, w / w) as the main emulsifier and polyethylene glycol 400 (16%, w / w) And ethanol (16%, w / w) as co-emulsifier to prepare sorafenib self-microemulsifying drug delivery system. The relative bioavailability of orally taken rats was determined. Results: The final concentration of sorafenib in the self-microemulsifying drug delivery system was 20 mg.mL-1. After emulsification, the preparation has a particle size of 20-25 nm and can be stably present in deionized water, normal saline and 5% glucose solution for 8 h. Compared with the sorafenib suspension, the self-microemulsifying drug delivery system can significantly increase the area under the plasma concentration-time curve (AUC0 ~ 72 h), peak concentration (Cmax) and average residence time of sorafenib MRT), reduce clearance (CL). In particular, its relative bioavailability is increased by about 25-fold compared to oral suspensions. Conclusion: Sorafenib self-microemulsifying drug delivery system can significantly increase the relative bioavailability of sorafenib oral absorption and is expected to be developed into a pharmaceutical preparation for increasing its oral absorption.