Development of an itraconazole-loaded gelatin microcapsule with enhanced oral bioavailability: physicochemical characterization and in-vivo evaluation

摘要

Objectives The aim of this study was to develop a novel itraconazole-loaded gelatin microcapsule without ethanol with enhanced oral bioavailability. Methods Various gelatin microcapsules were prepared using a spray-drying technique. Their physicochemical properties, dissolution, characteristics and pharmacokinetics in rats were evaluated and compared with those of a commercial product. Key findings The gelatin microcapsule at a weight ratio for itraconazole/gelatin/citric acid of 1 : 3 : 0.3 was spherical in shape with a smooth surface and inner hole, and gave a maximum drug solubility of about 700 mug/ml. The gelatin microcapsule dramatically increased the initial dissolution rate of itraconazole compared with a commercial product in simulated gastric fluids (pH 1.2). Moreover, at the same dose as the commercial product, it gave significantly higher initial plasma concentrations, C_(max) and AUC of itraconazole in rats than did the commercial product, indicating that providing the drug in the gelatin microcapsule caused enhanced absorption in rats. At half dose, it gave similar AUC, C_(max) and C_(max) values to the commercial product, suggesting that it was bioequivalent to the commercial product in rats. Conclusions The itraconazole-loaded gelatin microcapsule without ethanol developed using a spray-drying technique at half the dose of the commercial product can deliver itraconazole in a pattern that allows fast absorption in the initial phase, making it bioequivalent to the commercial product.