Investigation on utility of some novel terpenes on transungual delivery of terbinafine for the management of onychomycosis

Abstract

Introduction: Onychomycosis is a fungal disorder of the nail which afflicts 5% of the population worldwide. The disease is strenuous to cure as it is chronic, hard to eliminate and tends to recur. Topical therapy is at the forefront for the treatment of many disorders of nail. However, the success rate of topical therapy has been halted owing to the poor permeation of topical therapeutics across densely keratinized nail barrier. Therefore, ungual drug permeation must be improved for an effective topical therapy. An approach to achieve this goal would be the use of terpenes from natural sources as potential penetration enhancers. This study is aimed to explore the effectiveness of some novel terpenes as potential penetration enhancers on transungual delivery of terbinafine. Methods: Ex-vivo permeation studies were performed by sopping the nail clippings of healthy human volunteers in control and working solutions containing terbinafine (5mg/ml) per se and terbinafine (5mg/ml) with 6% of each terpenes including lavandulol, safranal, rose oxide, limonene, 3-methyl-2-butene-1-ol, and linalool respectively for 48 hours. The terbinafine concentration in nail samples was determined using a HPLC method. Results: Statistical analysis showed that studied terpenes increase transungual penetration of terbinafine in the following order: linalool > rose oxide > 3-methyl-2-butene-1-ol > safranal> limonene>lavandulol acetate. Accordingly, linalool was found to be the most effective penetration enhancer for the transungual delivery of terbinafine. Conclusion: It is concluded that linalool can be used as safe and potential penetration enhancer for enhancing the transungual delivery of terbinafine for onychomycosis.