The effect of penetration enhancers on the kinetics of percutaneous absorption

The effect of penetration enhancers on the kinetics of percutaneous absorption and transdermal drug delivery has been examined theoretically. Using a physically based pharmacokinetic description of skin absorption, the action of model promoters has been investigated as a function of the physicochemical properties of the penetrant. The kinetic simulation permits both zero- and first-order input of the drug from the delivery system; diffusion through the skin is modelled by consecutive transport steps across the stratum corneum and viable epidermis and by a partitioning process at the lipophilic-aqueous phase boundary between those two tissue layers. Two model enhancers, whose effects occur specifically in skin, are considered: the first (PE1) increases the drug diffusion coefficient (D_s) across the stratum corneum by an order of magnitude; the second (PE2) again increases D_s ten-fold but also reduces the effective stratum corneum-viable tissue partition coefficient of the drug to 10% of its unperturbed value. The action of these promoters is shown to be sensitive to the oil-water distribution characteristics of the drug: PE1 is effective for relatively hydrophilic compounds but becomes increasingly ineffectual as a drug lipophilicity increases (log K (moctanol/H₂O)≥2); PE2, on the other hand, provides little additional effect over PE1 for hydrophilic substances but significantly enhances the transdermal delivery of hydrophobic moieties. It appears, therefore, that the desirable properties of a penetration enhancer may change depending upon the physico-chemical nature of the drug being delivered.