Tavaborole microemulsion: New strategy for the targeted treatment of onychomycosis

Abstract

The targeted treatment of onychomycosis becomes a major concern nowadays for onychologist considering the limited permeability of the drug formulation at the nail site due to the number of factors such as complex barrier of keratin structure inside the nail layer, drug-keratin binding properties, as well as lack of availability of promising drug delivery system. In the present study, tavaborole-loaded novel microemulsion and its gel formulation was developed, optimized, and evaluated for the targeted treatment of onychomycosis. The microemulsion formulation was designed and developed using a 32 factorial experimental design approach. The optimized microemulsion formulation consisting of tavaborole (2.5%w/w), glyceryl caprylate/caprate (7.8%w/w), polyethylene glycol-8 caprylate/capric glycerides (21.45%w/w), diethylene glycol monoethyl ether (21.45%w/w) and demineralized water (46.80%w/w) was converted to gel using carbopol® 934P (0.5%w/w). In the ex-vivo bovine hoof membrane model permeation study, the optimized microemulsion formulation exhibited higher drug permeation (116.21 ± 9.75 μg/cm2) and followed the first-order release kinetics mechanism. The in-vitro nail clipping study demonstrated enhanced penetration of tavaborole (0.872 ± 0.019 μg/mg) from optimized microemulsion formulation. It also exhibited improved antifungal activity against dermatophytes species such as Trichophyton rubrum (2.56 ± 0.086 cm), Trichophyton mentagrophytes (3.13 ± 0.097 cm), and Candida albicans (3.63 ± 0.103 cm). The microemulsion formulation did not reveal any toxic and detrimental effects of excipients on nail cells in VERO cell lines cytotoxicity study. Thus, tavaborole loaded microemulsion can be considered as a potential formulation for topical onychomycosis therapy.