Transdermal therapeutic systems--actual state and future developments.

Modern transdermal therapeutic systems have been marketed since the last decade only. Nitroglycerin, scopolamine, clonidine, estradiol and nicotine are the current prominent representatives that have matched expectations regarding therapeutical benefits based on TTS applications. Although different TTS constructions have been realized, it is nevertheless appropriate to consider the governing role of the skin permanent. As the upper skin barrier limits flux rates, drug uptake has to be improved by the TTS's own occlusion or by flux enhancers. Enhancers act either on the hydrophilic keratin matrix or on the lipophilic intercellular material in the stratum corneum. Improvements in drug diffusion must be balanced carefully with the risk of skin irritation. In the future we should expect, among others, pulsatile systems to avoid tolerance, or systems comprising fixed combinations of transdermal drugs within one TTS, possibly at first in the field of hormones. Other expectations will be discussed. Therapeutic benefits are expected by the administration of highly potent topical drugs by means of TTS-analogous therapeutic systems, enabling a time-controlled drug release for purposes of topical treatment only.