Investigation of regional differences in transdermal drug delivery

The potential of transdermal drug delivery is substantial. However, the successful development of transdermal formulations as pharmaceutical products may be limited by anatomical site-specific variations in the barrier function, such variation is well documented and termed regional variation. ... The research described in this thesis demonstrates regional variation for a number of model permeants and CPEs, and highlights the complexities associated with defining the cause of variation with anatomical site. If the reasons for the differences in barrier between anatomical sites can be fully understood then it may be possible to minimise the variation with transdermal delivery systems. Such an understanding may also lead to means for increasing the bioavailability of drugs delivered by the transdermal route. Alternatively, enable the modulation of dosage simply by changing application sites. The findings may also be applied to understanding the risk of skin exposure to noxious chemicals such as pesticides. The variability observed in our results confirm the inherent variability and complexity of human skin, and we were cautious not to over interpret the data due to the limited number of donors for each of the anatomical sites investigated. Nevertheless, these results highlight the important role of physicochemical properties in determining permeation, and it is clear that transdermal formulations intended for clinical usage should be thoroughly evaluated for regional variation in a suitably powered study, particularly when novel permeants or permeation enhancers are involved.