Self-microemulsifying drug delivery system for improved oral bioavailability of oleanolic acid: design and evaluation

Abstract

Rui Yang,1 Xin Huang,1 Jinfeng Dou,2 Guangxi Zhai,2 Lequn Su1 1Pharmacy Department, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, People's Republic of China; 2Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, People's Republic of China Abstract: Oleanolic acid is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS) has been developed to enhance the solubility and oral bioavailability of oleanolic acid. The formulation design was optimized by solubility assay, compatibility tests, and pseudoternary phase diagrams. The morphology, droplet size distribution, zeta potential, viscosity, electrical conductivity, and refractive index of a SMEDDS loaded with oleanolic acid were studied in detail. Compared with oleanolic acid solution, the in vitro release of oleanolic acid from SMEDDS showed that the drug could be released in a sustained manner. A highly selective and sensitive high-performance liquid chromatography-mass spectrometry method was developed for determination of oleanolic acid in rat plasma. This method was used for a pharmacokinetic study of an oleanolic acid-loaded SMEDDS compared with the conventional tablet in rats. Promisingly, a 5.07-fold increase in oral bioavailability of oleanolic acid was achieved for the SMEDDS compared with the marketed product in tablet form. Our studies illustrate the potential use of a SMEDDS for delivery of oleanolic acid via the oral route. Keywords: oleanolic acid, self-microemulsifying drug delivery system, formulation design, in vitro release, bioavailability