Mucoadhesive Hydrogel Films of Econazole Nitrate: Formulation and Optimization Using Factorial Design

The mucoadhesive hydrogel film was prepared and optimized for the purpose of local drug delivery to oral cavity for the treatment of oral Candidiasis. The mucoadhesive hydrogel film was prepared with the poly(vinyl alcohol) by freeze/thaw crosslinking technique. 32 full factorial design was employed to optimize the formulation. Number of freeze/thaw cycles (4, 6, and 8 cycles) and the concentration of the poly(vinyl alcohol) (10, 15, and 20%) were used as the independent variables whereas time required for 50% drug release, cumulative percent of drug release at 8th hour, and “ ” of zero order equation were used as the dependent variables. The films were evaluated for mucoadhesive strength, in vitro residence time, swelling study, in vitro drug release, and effectiveness against Candida albicans. The concentration of poly(vinyl alcohol) and the number of freeze/thaw cycles both decrease the drug release rate. Mucoadhesive hydrogel film with 15% poly(vinyl alcohol) and 7 freeze/thaw cycles was optimized. The optimized batch exhibited the sustained release of drug and the antifungal studies revealed that the drug released from the film could inhibit the growth of Candida albicans for 12 hours. 1. Introduction Oral candidiasis is an infectious condition caused by the fungus of the genus Candida, the most common of which is Candida albicans. Oral candidiasis significantly occurs to the immunocompromised individuals, namely, patients with AIDS immunosuppression, cancer chemotherapy/radiation therapy, corticosteroid therapy, and chronic antibiotic therapy and individuals with xerostomia and diabetes mellitus [1, 2]. Chronic systemic administration of antifungal agents is required to treat the oral candidiasis, which may produce potential adverse effects. Therefore local administration of the antifungal agent is considered as the first line treatment for the oral candidiasis if the drug concentration remained above the minimum inhibitory concentration throughout the treatment [3]. It is difficult to achieve by the conventional dosage forms like oral gels, pastes, solution, suspensions, ointments, mouthwashes, lozenges, mouth paints, and so forth, because less retention time of the dosage form leads to the fluctuation in the salivary drug concentration [1, 2]. Therefore an ideal dosage form for the treatment of the oral candidiasis is one which sustains the release of drug and retains in the oral cavity and produce antifungal effect for prolonged period of time [4]. This is possible if the drug delivery system possesses sustained release as well as mucoadhesive