Evaluation of the porosity, the tortuosity, and the hindrance factor for the transdermal delivery of hydrophilic permeants in the context of the aqueous pore pathway hypothesis using dual‐radiolabeled permeability experiments

The aqueous pore pathway hypothesis has been modified to include both transient and steady‐state domains of diffusive transport to evaluate the porosity, the tortuosity, and the hindrance factor of the skin aqueous pore channels from an individual dual‐radiolabeled permeability experiment. Using these theoretical and experimental methods, the porosity (ε), the tortuosity (τ), and the hindrance factor (H) of the skin aqueous pore channels were evaluated as a function of: (i) the radius of the selected model hydrophilic permeants (urea, mannitol, raffinose, and inulin), and (ii) the extent of skin perturbation present in untreated skin, skin pretreated at a low dose, and a high dose, with a simultaneous application of 20 kHz ultrasound and the surfactant sodium lauryl sulfate (SLS), and the dermis. The results of this investigation revealed that the tortuosity decreased, and only the hindrance factor for inulin was significantly less than 1, over the range of permeant radii examined. Furthermore, only the porosity increased over the range of skin perturbation examined (over 100‐fold), suggesting that a surface‐related phenomenon is primarily responsible for the observed enhancement in the transdermal permeability of hydrophilic permeants induced by the simultaneous application of ultrasound and SLS. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 3263-3282, 2007