Transungual iontophoresis of lithium and sodium: effect of pH and co-ion competition on cationic transport numbers

Abstract

Iontophoresis has been proposed as an alternative method to deliver drugs into and across the nail plate. However, the knowledge about the rules governing transungual iontophoretic transport numbers is still uncomplete. This work investigated the iontophoretic and passive transungual fluxes of sodium and lithium and the effect of pH and co-ion competition on the cations' transport numbers. The objective was to further investigate whether nails show cation permselectivity at physiological pH and to improve our understanding of transport numbers during transungual iontophoresis. The donor solutions comprised the single ion and binary mixtures of the two cations at different pH. Sodium and lithium iontophoretic fluxes showed low inter-nail variability and were significantly greater than passive fluxes. Cationic transport numbers clearly increased as the pH was sequentially raised from 4.0 to 5.0 and then to 7.0, in agreement with a net negative charge of the human nails at physiological pH. Sodium transport number was maximal when the ion was formulated as a single ion (absence of competing co-ions) and decreased as the molar fraction of lithium was increased in the vehicle. The magnitude of the transport numbers measured and their response to changes in the cations' molar fraction and pH in the donor solution were remarkably similar to those observed during the transdermal iontophoresis. The ratio of lithium and sodium transport numbers was directly proportional to their relative concentration ratios; the proportionality constant being remarkably similar in the 4.0-7.0 pH range as well as to the ratio of the cations' aqueous mobilities. Another interesting similarity with transdermal iontophoresis was the existence of a cationic transport number threshold. On the whole, this work provided some key information about nail permselectivity and transungual transport numbers which will assist to formulate efficiently therapeutic compounds to be delivered iontophoretically into and across the nail plate.