ABSTRACT
Challenges in transdermal drug delivery are largely associated with the impermeability of the skin barrier. The stratum corneum, the uppermost epidermal layer of the skin comprising a matrix of highly ordered lipid lamellae, serves as the principal barrier to the permeation of chemicals that come in contact with the skin. In addition to the matrix composition, the tortuosity of the intercellular pathways through the stratum corneum also limits the ingress of permeants. Passive transdermal drug delivery is generally limited to lipophilic and low molecular weight compounds (1,2). ALZA Corporation (Mountain View, CA) has explored strategies to enhance skin permeability for a wide array of compounds through the use of chemical permeation enhancers, an electric field to facilitate transport of charged molecules, and mechanical formation of microscopic transport channels through the skin to deliver, in particular, high molecular weight compounds (3-5). This review focuses on three ALZA-developed transdermal delivery technologies: (i) D-TRANS incorporates means to improve, sustain, and
control passive transdermal transport, (ii) E-TRANS uses low levels of electrical current to actively transport a broad range of drugs through intact skin, and (iii) Macroflux creates superficial pathways through the skin barrier allowing transport of macromolecules.
