[Aspects of tolerance to transdermal systems from the dermatologic viewpoint]

If active drugs are required to penetrate the skin in order to reach the systemic circulation the integrity of the skin has to be impaired. The nature of the horny layer which, as the uppermost barrier takes over the main part of the protective function of the skin against all locally applied substances, is shortly outlined. It is demonstrated that inactive ingredients of transdermal therapeutic systems should induce only the minimum irritation of the horny layer which is absolutely necessary for the action of the system. A good tolerance seems to be granted only if an occlusion at all events is of a short duration, and the sebum deficiency and the vulnerability of the aging skin as well as the xerosia and residual syndets in the horny layer after frequent washing, baths or showers are taken into account. Furthermore, the potential risk for skin sensitization is discussed as each patch application can primarily induce a sensitizing potential for the applied active or inactive ingredient, which possibly may cause a contact eczema on repeated therapy. However, only a wide application and unfortunately not the clinical trial will supply detailed information on this aspect of risk.