transepithelial transport and in vivo oral absorption of simvastatin

13 Abstract 14 This study compared formulation effects of a dendrimer and a liposome preparation on the water solubility, transepithelial transport, and 15 oral bioavailability of simvastatin (SMV). Amine-terminated G5 PAMAM dendrimer (G5-NH2) was chosen to form SMV/G5-NH2 16 molecular complexes, and SMV-liposomes were prepared by using a thin film dispersion method. The effects of these preparations on the 17 transepithelial transport were investigated in vitro using Caco-2 cell monolayers. Results indicated that the solubility and transepithelial 18 transport of SMV were significantly improved by both formulations. Pharmacokinetic studies in rats also revealed that both the SMV/G519 NH2 molecular complexes and the SMV-liposomes significantly improved the oral bioavailability of SMV with the liposomes being more 20 effective than the G5-NH2. The overall better oral absorption of SMV-liposomes as compared to SMV/G5-NH2 molecular complexes 21 appeared to arise from better liposomal solubilization and encapsulation of SMV and more efficient intracellular SMV delivery. 22 © 2015 Published by Elsevier Inc.