Research and preparation of solid dispersion of itraconazole in hydroxypropyl-beta-cyclodextrin

Abstract

Itraconazole (ITZ) is an oral antifungal drug belongs to triazole group. However, ITZ has low and pH denpendant water solubility of about 1.1μg/ml at pH 6.8 and 6μg/ml at pH 1. Increasing solubility of ITZ is thus an urgent step for enhancement its bioavailability. Solid dispersions of ITZ and HPβCD were prepared by various methods: dry grindind, wet grinding and co-evaporation solvent with different molar rations of ITZ: HPβCD (1:1, 1:2, 1:3). Solid dispersion ITZ- HPβCD were evaluated by water solubility, dissolution profile in gastric medium. Physical characteristics of ITZ-HPβCD were assessed by DSC and FTIR spectrum. Dissolution test of solid dispersioncontaining hard capsule was also experimented. Solid dispersions formulated based on dry grinding and wet grinding method showed high solubility but low dissolution profile (<20%). Solid dispersion formulation based on co-evaporation solvent showed high dissolution profile. Dissolution profile of solid dispersion-containing hard capsule showed high ITZ release after 10 mins and reach over 80% after 15 mins.