Effect of a novel penetration enhancer on the ungual permeation of two antifungal agents.

OBJECTIVES The aim of this study was to demonstrate the effect of a novel permeation enhancer system using two existing marketed nail lacquers and the delivery of terbinafine through human nail samples in vitro. METHODS Initially a modified Franz cell was used, where sections of human nail serve as the barrier through which drug penetrates into an agar-filled chamber infected with dermatophytes. A second study was performed using a novel infected nail model where dermatophytes are incubated with and grow into human nail and ATP levels are used as biological marker for antimicrobial activity. KEY FINDINGS The novel permeation enhancing system increased the permeation of both existing drugs formulated in nail lacquers and terbinafine through human nail sections mounted in a modified Franz cell. Furthermore the ATP assay confirmed that the system also enhanced the permeation of terbinafine through infected cadaver nail resulting in a decrease in ATP levels equivalent to those of uninfected negative control samples. CONCLUSIONS This study has clearly demonstrated that the use of a novel permeation enhancing system, which fundamentally alters the chemical structure of the nail, not only enhances the efficacy of the existing topical formulations but also enables the delivery and efficacy of terbinafine when applied ungually. Such a topically applied system has the possibility of overcoming the systemic side effects when terbinafine is delivered orally.