Formulation development and evaluation of semisolid preparation of antifungal drug: Itraconazole

Itraconazole (ITZ) is a synthetic triazole antifungal agent that is active against a broad spectrum of fungal species and effective for the treatment of both systemic fungal infections and superficial mycoses. Sporanox® capsule, oral solution and injection (Janssen Pharmaceutical) are the only commercialized product of itraconazole. The absolute bioavailability of oral ITZ is 55% (±15%) and reduced by 40% when it is administered under fasting conditions. In the present work various semisolid formulations of ITZ were developed for topical use with the objective to improve its therapeutic efficacy, patient compliance and to reduce the frequency of dosing and side effects, as well as to avoid its extensive first pass metabolism. Total six semisolid formulations belonging to ointment, cream and gel were prepared and evaluated for various physicochemical parameters like pH, drug content, rheological properties, in vitro drug release and ex vivo drug permeation. The selected formulation from the results of above mentioned evaluation tests was further subjected to skin irritation test on rabbit, antifungal activities and accelerated stability study. It was observed that pH and drug content of all formulations were in limit. Formulation F4 showed the highest in vitro drug release and ex vivo permeation among all the formulations. The in vitro release from all formulations followed Higuchi's diffusion mechanism. No irritation was observed by skin irritation test. It can be concluded that HPMC gel containing ITZ can extend the release of drug for longer period and has wider prospect for topical preparations.