Alteration of the diffusional barrier property of the nail leads to greater terbinafine drug loading and permeation.

The diffusional barrier property of biological systems varies with ultrastructural organization of the tissues and/or cells, and often plays an important role in drug delivery. The nail plate is a thick, hard and impermeable membrane which makes topical nail drug delivery challenging. The current study investigated the effect of physical and chemical alteration of the nail on the trans-ungual drug delivery of terbinafine hydrochloride (TH) under both passive and iontophoretic conditions. Physical alterations were carried out by dorsal or ventral nail layer abrasion, while chemical alterations were performed by defatting or keratolysis or ionto-keratolysis of the nails. Terbinafine permeation into and across the nail plate following various nail treatments showed similar trends in both passive and iontophoretic delivery, although the extent of drug delivery varied with treatment. Application of iontophoresis to the abraded nails significantly improved (P<0.05) TH permeation and loading compared to abraded nails without iontophoresis or normal nails with iontophoresis. Drug permeation was not enhanced when the nail plate was defatted. Keratolysis moderately enhanced the permeation but not the drug load. Ionto-keratolysis enhanced TH permeation and drug load significantly (P<0.05) during passive and iontophoretic delivery as compared to untreated nails. Ionto-keratolysis may be more efficient in permeabilization of nail plates than long term exposure to keratolysing agents.