title: Combined use of phospholipid complexes and self-emulsifying microemulsions for improving the oral absorption of a BCS class IV compound, baicalin.
abstract: The aim of this study was to develop a formulation to improve the oral absorption of baicalin (BA) by combining a phospholipid complex (PC) and self-emulsifying microemulsion drug delivery system (SMEDDS), termed BA-PC-SMEDDS. BA-PC was prepared by a solvent evaporation method and evaluated by complexation percentage (CP). The physicochemical properties of BA-PC were determined. The synergistic effect of PC and SMEDDS on permeation of BA was studied in vitro with Caco-2 cells and in situ with a single pass intestinal perfusion model. The improved bioavailability of BA in BA-PC-SMEDDS was confirmed in an in vivo rat model. The CP of BA-PC reached 100% when the molar ratio of drug to phospholipid (PP) was ≥1:1. The solubility of BA-PC increased in both water and octanol, and the log P o/w of BA-PC was increased significantly. BA-PC-SMEDDS could be dispersed more evenly in water, compared to BA and BA-PC. Both the Caco-2 cell uptake and single-pass intestinal perfusion models illustrated that transport of BA in BA-PC was lower than that of free BA, while improved significantly in BA-PC-SMEDDS. The relative bioavailability of BA-PC(1:2)-SMEDDS was 220.37%. The combination system of PC and SMEDDS had a synergistic effect on improving the oral absorption of BA.
authors.affiliation: School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Huiyi
authors.initials: H
authors.lastname: Wu
authors.affiliation: School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Long
authors.affiliation: School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yuan
authors.affiliation: School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Sujing
authors.initials: S
authors.lastname: Pan
authors.affiliation: School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Yunjun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, Thomas J Long School of Pharmacy & Health Sciences, University of the Pacific, CA 95211, USA.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Stowell
authors.affiliation: Department of Pharmaceutics, Thomas J Long School of Pharmacy & Health Sciences, University of the Pacific, CA 95211, USA.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
keywords: Baicalin; Bioavailability; Caco-2 cell; Phospholipid complex; SMEDDS; Single-pass intestinal perfusion