Self-microemulsifying drug-delivery system for improved oral bioavailability of probucol: preparation and evaluation

Abstract

Xianyi Sha, Juan Wu, Yanzuo Chen, Xiaoling FangKey Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education and PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, ChinaAbstract: The objective of our investigation was to design a self-microemulsifying drug-delivery system (SMEDDS) to improve the bioavailability of probucol. SMEDDS was composed of probucol, olive oil, Lauroglycol FCC, Cremophor EL, Tween-80, and PEG-400. Droplet sizes were determined. In vitro release was investigated. Pharmacokinetics and bioavailability of probucol suspension, oil solution, and SMEDDS were evaluated and compared in rats. Plasma drug concentration was determined by high-performance liquid chromatography. After administration of probucol suspension, plasma drug concentration was very low. Relative bioavailability of SMEDDS was dramatically enhanced in an average of 2.15- and 10.22-fold that of oil solution and suspension, respectively. It was concluded that bioavailability of probucol was enhanced greatly by SMEDDS. Improved solubility and lymphatic transport may contribute to the enhancement of bioavailability.Keywords: self-microemulsifying drug-delivery system (SMEDDS), probucol, bioavailability