Abstract
Since the introduction of the first through the skin (TTS) therapeutic in 1980, a total of 34 TTS products have been marketed and numerous drugs have been tested by more than 50 commercial organisations for their suitability for TTS delivery. Most of the agents which have been tested have had low molecular weights, due to the impermeability of the skin barrier. This barrier resides in the outermost skin layer, the stratum corneum. It is mechanical, anatomical, as well as chemical in nature; laterally overlapping cell multi-layers are sealed by tightly packed, intercellular, lipid multi-lamellae. Chemical skin permeation enhancers increase the transport across the barrier by partly solubilising or extracting the skin lipids and by creating hydrophobic pores. This is often irritating and not always well-tolerated. The TTS approach allows drugs (< 400 kDa in size) to permeate through the resulting pores in the skin, with a short lag-time and subsequent steady-state period. Drug bioavailability for TTS delive...