Formulation issues

After cutaneous administration of formulations such as ointments or creams, drug, vehicle, and the skin may affect the penetration process and thus drug action in different ways. Tronnier’s triangle (Fig. 1) (1) serves as model to illustrate these relationships. Drug and vehicle are the components of cutaneous formulations, which may be divided into those intended for transdermal absorption and systemic action of the drug, those for regional effects in deeper tissue layers (e.g., joints) and those for action on or in the skin (local action) (2). Formulations intended for systemic drug action require therapeutic plasma levels of the drug. The use of transdermal patches, which remain on the skin for an extended period of time, allows in most cases a zero-order drug input kinetic and thus constant plasma levels over the whole application time period (3). While formulations with regional action require drug penetration into deeper skin tissues with minimal systemic action, for formulations with local action systemic action is undesired. In the latter case, drug penetration into the skin may be slow but accompanied by a high substantivity.