Preparation and evaluation of dual-mode floating gastroretentive tablets containing itraconazole

Abstract

The aims of the present study were to prepare new dual-mode floating gastroretentive tablets (DF-GRT) containing itraconazole (ITR) and to evaluate influence of the dosage forms on pharmacokinetic parameters of ITR. The solubility of ITR was enhanced around 200 times (from 1.54 to 248.38 mu g/mL) by preparing solid dispersion (SD) with hydroxypropylmethyl cellulose. Buoyancy of DF-GRT containing ITR-SD was established by both camphor sublimation and gas generation. Camphor sublimation decreased density of DF-GRT by making pores in tablet matrix, which led to elimination of lag time for floating. Carbon dioxide generated by sodium bicarbonate and citric acid helped to maintain buoyancy of DF-GRT. Therefore DF-GRT floated on the medium without lag time until disintegrated entirely during in vitro release study. They released 89.11% of the drug at 2 h. Residual camphor was <0.5 wt% after sublimation. The pharmacokinetics of DF-GRT was evaluated in six miniature pigs and compared to immediate release tablets (IRT). Mean AUC ratio of GRT/IRT was 1.36 but there was no statistical difference between AUC values. However delayed t(max), increased MRT and equivalent C-max of DF-GRT supposed it could be a promising tool for gastroretentive drug delivery system containing ITR.