Preparation and characterization of the inclusion complex of ursolic acid with polymerized hydrophilic cyclodextrin

Ursolic acid is a natural triterpenoid with a broad spectrum of biological activity. Its clinical application is limited due to poor aqueous solubility. The aim of present work was to prepare an inclusion complex of ursolic acid, a pentacyclic triterpenoid with polymerized hydrophilic derivative of β-cyclodextrin [epichlorohydrin beta cyclodextrin (Epi-β-CD)] to improve its apparent solubility, dissolution rate and stability. The solubility was evaluated by phase solubility method of Higuchi's and the profile displayed a typical AL-type curve, indicating the formation of 1:1 stoichiometric binary inclusion complex. The inclusion complex was prepared by freeze-drying and characterized by analytical techniques XRD, DSC, FTIR, drug content and in-vitro release study. The results suggested that ursolic acid could form true inclusion complex with epi-β-CD and was deeply included in the cavity of epi-β-CD. Additionally, the dissolution rate and stability of the inclusion complex were greatly improved compared with the pure drug. Thus, the use of polymerized cyclodextrins would be a promising approach to improve the physicochemical characteristics of natural triterpenoids.