Passive enhancement strategies in topical and transdermal drug delivery

The skin has an extremely good barrier function and to improve topical bioa vailability it is usually necessary to employ enhancement strategies. Optim ization of the applied formulation can improve release to the skin and the use of supersaturation achieves this objective. However, supersaturated sta tes are inherently unstable. High solvent concentrations in the formulation may remove skin lipids reducing the barrier function of the stratum corneu m. Alternatively formulation components can diffuse into the barrier functi on 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 solv ent into the viable tissue may also result in increased drug concentrations in this layer of the epidermis. The viable layer is metabolically very act ive and perturbation of the enzyme systems responsible for the formation of the stratum corneum lipids can reduce the barrier function. Finally a diff using drug will encounter the blood supply. If vasoactive drugs modulate th e blood flow rate, absorption can be influenced. (C) 1999 Elsevier Science B.V. All rights reserved.