Development and evaluation of a topical film forming spray of Ketoconazole for fungal infection treatment

Background: To treat superficial fungal diseases including Tinea corporis, Tinea cruris, and Tinea pedis, the current study set out to create and assess a novel film-forming spray (FFS) containing Ketoconazole. Traditional topical formulations frequently have drawbacks such skin irritation, frequent reapplication, and poor retention. Eudragit RS100 and ethyl cellulose were used as film-forming polymers in a eutectic mixture of camphor and menthol to create an FFS in order to get around these problems. The formulation was optimized using a 3² factorial design. Drug content, film flexibility, stickiness, evaporation time, pH, viscosity, and in vitro drug diffusion were all assessed for the produced formulations. Among all batches, formulation F5 showed the most promising results, with a drug content of 96.6%, excellent film properties, and the highest cumulative drug release of 94.5% over 720 minutes. The film was flexible, non-sticky, and resistant to wash-off. These findings suggest that the developed film-forming spray provides sustained drug release, improved patient compliance, and effective management of superficial fungal infections. Objective: The objective of the present study was to develop and evaluate a novel topical film-forming spray of Ketoconazole for the treatment of superficial fungal infections. The formulation was designed to overcome the drawbacks of conventional topical dosage forms such as poor skin retention, frequent reapplication, and irritation. The study focused on preparing a spray using Eudragit RS100 and ethyl cellulose as film-forming polymers, along with a eutectic mixture of camphor and menthol to enhance permeation and patient comfort. The formulation was optimized using a factorial design and evaluated for physicochemical properties, film characteristics, in-vitro drug release, and antifungal activity in order to ensure sustained release, improved patient compliance, and effective therapeutic action. Methods: The film-forming spray of Ketoconazole was prepared using Eudragit RS100 and ethyl cellulose as film-forming polymers, with a eutectic mixture of camphor and menthol serving both as a permeation enhancer and soothing agent. Ketoconazole was dissolved in a solvent system of ethanol and acetone, followed by the incorporation of polymers under continuous stirring. PEG 400 and glycerine were added as plasticizers to improve film flexibility. The prepared solution was sonicated to ensure uniformity and then filled into spray containers with dip tubes for ease of application. The formulations were optimized using a 3² factorial design by varying the concentrations of the polymers, and the prepared batches were evaluated for appearance, pH, viscosity, evaporation time, drug content, film-forming ability, flexibility, stickiness, washability, in-vitro drug release using Franz diffusion cell, and antifungal activity by agar well diffusion method. Findings: The developed Ketoconazole film-forming spray showed desirable physicochemical characteristics, including suitable pH within the skin range, optimum viscosity, and rapid evaporation time leading to uniform film formation. The prepared films were flexible, non-sticky, and resistant to wash-off, ensuring better skin adherence compared to conventional topical formulations. In-vitro diffusion studies confirmed sustained drug release, with formulation F5 exhibiting the most balanced release profile, delivering 94.5% cumulative drug release over 12 hours. The antifungal study demonstrated significant activity, where the spray produced a zone of inhibition comparable to that of a marketed Ketoconazole cream despite containing a lower drug concentration, indicating enhanced local drug delivery and prolonged retention at the site of infection. Conclusion: The study successfully developed and evaluated a Ketoconazole-based film-forming spray as a novel topical formulation for superficial fungal infections. The optimized formulation (F5) exhibited excellent physicochemical stability, sustained drug release, and strong antifungal activity, along with advantages such as improved retention, reduced dosing frequency, and better patient compliance. These findings suggest that the filmforming spray can serve as a promising alternative to conventional creams and ointments for effective management of superficial fungal infections.