Preparation and Optimization of Voriconazole Gel 0.25% for Topical Delivery in Terbinafine Resistance Dermatophytosis: In Vitro and Pilot Animal Study

伏立康唑0.25%凝胶的制备和优化及其在特比萘芬耐药性皮肤癣菌病局部给药中的应用:体外和初步动物研究

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Abstract

BACKGROUND: There have been several reports of patients with chronic recalcitrant diseases, rare presentations, recurrent relapses, and treatment failure. This study aimed to formulate and evaluate the safety profile of topical voriconazole (VCZ) gel 0.25% for effective drug delivery to the skin as an adjuvant therapy in cases of extensive dermatophytosis. METHODS AND MATERIALS: VCZ 0.25% topical gel was manufactured by Carbomer, and its characteristics such as pH, viscosity, density, and microbial growth were examined at 40 ± 2°C/75 ± 5% RH for six months. The animals were divided into three groups (2:2:2) randomly. The hair from the back of guinea pigs (test sites: 2 cm(2)) was shaven, and their skin was scraped slightly using a single-use scalpel. Afterward, terbinafine drug-resistant Arthroderma benhamiae suspension (50 μL) was inoculated to a 2 cm(2) surface area of the shaven skin. RESULTS: Agar culture of scrapings from the area indicated the infection development. The fabricated VCZ topical gel exhibited acceptable stability. The VCZ 0.25% gel was proved to be an effective treatment in a time-dependent base, in comparison with terbinafine (1%) as a positive control (p < 0.05). Furthermore, using gel base VCZ 0.25% reduced the period of full treatment of A. benhamiae infection to five days, compared with the 12-day complete cure by terbinafine. CONCLUSION: Results from the present study indicated that gel-based VCZ could be utilized as topical therapy for dermatophytosis. Due to the increase of drug-resistant dermatophyte spp., indications of gel base VCZ 0.25% for treating dermatophytosis are believed to increase accordingly.

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