Passive enhancement strategies in topical and transdermal drug delivery

The skin has an extremely good barrier function and to improve topical bioavailability it is usually necessary to employ enhancement strategies. Optimization of the applied formulation can improve release to the skin and the use of supersaturation achieves this objective. However, supersaturated states are inherently unstable. High solvent concentrations in the formulation may remove skin lipids reducing the barrier function of the stratum corneum. Alternatively formulation components can diffuse into the barrier function where they can have two distinct effects. They may intercalate into the structured lipids of the bilayer, decreasing their diffusional resistance. Alternatively they can modify the solubility parameter of the skin lipids; the diffusing drug may then have an enhanced solubility in the skin. If the two effects can be combined synergy is observed. Deeper permeation of solvent into the viable tissue may also result in increased drug concentrations in this layer of the epidermis. The viable layer is metabolically very active and perturbation of the enzyme systems responsible for the formation of the stratum corneum lipids can reduce the barrier function. Finally a diffusing drug will encounter the blood supply. If vasoactive drugs modulate the blood flow rate, absorption can be influenced. (C) 1999 Elsevier Science B.V. All rights reserved.