Antifungal potential of tolnaftate against Candida albicans in the treatment of onychomycosis: development of nail lacquer and ex vivo characterization

Onychomycosis, a chronic fungal infection of nail plate and nail bed is a most emerging disease of finger/toe nail nowadays. It accounts for approximately 50% of all nail diseases and is the most common disorder in adults. Treatment of onychomycosis relies widely on longduration systemic/oral antifungal therapy, which is often associated with serious side effects, drug interactions, and high recurrence rates (1). Enhanced survey on the prevalence of the disease as well as inventions of newer antifungal agents resulted in higher concern among the patients to get cure of the disease and also among medical practitioners to constitute an effective therapy. However, there has been an issue regarding the treatment which may be prescribed without prior knowledge of infection. The effectiveness of several antifungals against the fungi is not well understood and drugs are often recommended for inappropriate time periods (2). Therefore, the treatment of onychomycosis is a challenging task as the infection is embedded within the nail (3). Antifungals are available in market in the form of cream, ointment, lotion, powder, and solutions. These formulations require high concentration of active agents to be incorporated for effective therapy because of their low efficacy. To overcome the limitations of conventional formulations there is a need of an effective system that can deliver the antifungals deep into the nail bed. However, the development of a formulation for safe and effective topical delivery in the treatment of onychomycosis is still under infancy. Topical therapy would be an attractive alternative approach in the treatment of onychomycosis as it is found to be capable of overcoming most of the limitations of systemic administration and targeting the drug at its site of action, with minimum interactions and adverse effects. Limited permeability of the drug Abstract Onychomycosis constitutes the most common fungal infection of nail affecting finger and toe nails as well. Antifungals found to be effective in the treatment of onychomycosis. However, transport of oral antifungal agents exhibits more toxicity and requires longer treatment period. Medicated nail lacquers proved to cause lesser toxicity and required shorter treatment period. It provides not only finger/toe nail infection therapy and but also act as a protection for nails. Thus, the objective behind the present investigation was to develop nail lacquer for transungual delivery of tolnaftate. Its potency had been assessed by evaluating penetration efficiency across the bovine hoof membrane. Preliminary studies aided the optimization of thioglycolic acid as permeation enhancer (HEFmax 0.60 ± 0.377) and menthol as local anaesthetic. n-butanol:isopropyl alcohol with optimum drying time of 60 sec was selected as optimum solvent system. In total nine formulations were developed based on 3 full factorial design and characterized for drying time, non-volatile content, in vitro adhesion and permeation study. Based on highest desirability, F6 was selected as an optimized formulation and evaluated for viscosity, stability and antifungal activity. Optimized formulation exhibited optimum viscosity and stability for 1 month period. Better antifungal activity was observed against Candida albicans in comparison to the control formulation. Thus, it can be concluded from the investigation that nail lacquer could proved to be a better alternative for transungual delivery of tolnaftate.