ABSTRACT
Although the skin is the most accessible organ, it is in many ways one of the most difficult to treat. This is because it has evolved to prevent the loss of water and also the ingress of xenobiotics. There are reports in the ancient Egyptian literature on the use of agents to treat the skin and some 4000 years later we are still investigating the precise nature of the barrier function (1). It is possible now to use sophisticated and sensitive techniques to examine the barrier properties at a molecular level and to use this information to optimize the structure of the drug to be delivered and the formulation in which it is presented. Unfortunately it is not as simple as this and many actives that are used on the skin, either for dermal or transdermal use, were not originally developed with the target of the skin in mind. This means that often they have the wrong characteristics for dermal delivery and it is only with judicious formulation that some activity is produced. Even though it has been known for many years that skin bioavailability is only of the order of a few percent (2) there have been few attempts to discover what happens to the rest of the applied drug.
