Water diffusivity in human nail plate

The diffusivity of water in human nail at 32°C was determined for cadaveric, human finger nails having water contents ranging from 0.536 g H2O/g dry nail to 0.035 g H2O/g dry nail by measuring the desorption of tritiated water from nails suspended in water or in the vapor phase above salt solutions yielding a range of relative humidities (RH). Diffusivity increased with increasing RH from (7.7 ± 1.3) × 10−10 cm2 s−1 at 15% RH to (3.2 ± 1.1) × 10−7 cm2 s−1 in the liquid phase study at 100% RH, a more than 400‐fold increase. The diffusivity values, which may be understood in terms of the equilibrium water content of the nail and a free volume theory for diffusion in hydrophilic polymers, were consistent with water diffusivities measured in other keratinized tissues including wool, horn and the corneocyte phase of stratum corneum. Analysis of the tritium desorption data was complicated by a tritium exchange process between 3H2O and nail keratin, the kinetics of which are presented in part. The combination of the concentration‐dependent water diffusivity with the natural water activity gradient in nail in vivo leads to the prediction of a nonlinear steady‐state water concentration profile in human nail in vivo which, in turn, has implications for ungual drug delivery. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 3352-3362, 2007