Influence of pH on Transungual Passive and Iontophoretic Transport

The present study investigated the effects of pH on nail permeability and the transport of ions such as sodium (Na) and chloride (Cl) ions endogenous to nail and hydronium and hydroxide ions present at low and high pH, which might compete with drug transport across hydrated nail plate during iontophoresis. Nail hydration and passive transport of water across the nail at pH 1-13 were assessed. Subsequently, passive and iontophoretic transport experiments were conducted using Na-22 and Cl-36 ions under various pH conditions. Nail hydration was independent of pH under moderate pH conditions and increased significantly under extreme pH conditions (pH >11). Likewise, nail permeability for water was pH independent at pH 1-10 and an order of magnitude higher at pH 13. The results of passive and iontophoretic transport of Na and Cl ions are consistent with the permselective property of nail. Interestingly, extremely acidic conditions (e.g., pH 1) altered nail permselectivity with the effect lasting several days at the higher pH conditions. Hydronium and hydroxide ion competition in iontophoretic transport was generally negligible at pH 3-11 was significant at the extreme pH conditions studied. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:1955-1967, 2010