Preparation Physicochemical Characterization and In-vitro Dissolution Studies of Diosmin-cyclodextrin Inclusion Complexes

摘要

Diosmin, a vascular-protecting agent, is practically insoluble in water, and its oral absorption is limited by its extremely low dissolution rate. In this study, β-cyclodextrin (βCD) and 2-hydroxypropyl-β-cyclodextrin (HPβCD) were obtained to improve the solubility and dissolution rate of diosmin. Phase solubility studies of diosmin with βCD and HPβCD in distilled water were conducted to characterize the complexes in liquid state. The solid-state characterization of the complexes prepared with different methods was performed by fourier transform-infra red spectroscopy (FTIR), optical microscopy analyses, and differential scanning calorimetry (DSC). Dissolution studies were carried out in distilled water using US pharmacopeia dissolution rate testing equipment. The complexation of diosmin with βCD and HPβCD both indicated an AL type of phase-solubility diagrams, and the apparent stability constants (Kc) was found to be 222.13 and 200.08 M⁻¹, respectively. The Kc values indicated the βCD and HPβCD showed the similar equal complexation ability with diosmin, HPβCD provided higher solubility for diosmin due to its higher water solubility. The dissolution studies suggest that the inclusion complexes provide higher dissolution rate compared with the physical mixtures and the drug alone. Furthermore, the inclusion complex prepared by freeze drying method presented higher dissolution rate than kneading method.