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Background Onychomycosis is a common disease. Topical treatment is usually not effective due to limitation of trans-nail delivery of antifungal drugs. Successful treatment of deep-seated nail infections remains elusive as the delivery of efficacious levels of antifungal drug to the site of action is very difficult. Objectives To evaluate the influence of several parameters including; the effect of low electrical current, incubation time and the presence of electrolyte (NaCl or KCl) on the penetration of terbinafine through the nail plate into the nail bed, using various formulations and concentrations of terbinafine HCl. Methods Iontophoresis was applied across porcine and human nail in vitro to assess its efficiency in enhancing delivery of terbinafine HCl. Results In this study, we have demonstrated that an optimal electrolyte concentration (1% NaCl or KCl) is required for an effective delivery. There is a significant increase in drug delivery into the nail and into the receiving compartment in the presence of 3% DMSO. Conclusions This study demonstrates the efficacy of iontophoresis in enhancing the trans-nail delivery of terbinafine. Clinical studies are needed to evaluate the feasibility, efficacy and safety of iontophoresis of terbinafine in onychomycosis in human.