The stratum corneum (SC), the outermost layer of the skin, presents a formi
dable barrier to transdermal drug delivery. As a result, different strategi
es have been developed to enhance drug transport into and through skin. Ion
tophoresis involves the application of a small electrical current which dri
ves molecules across the skin and controls relatively well the rate of deli
very. Although the technique has been widely investigated in-vitro, the eva
luation of skin integrity in-vivo after iontophoresis is absolutely necessa
ry for the future clinical application of this approach. This paper reviews
the non-invasive biophysical techniques which have been used to assess the
effects of current application on human skin in-vivo. Specifically, transe
pidermal water loss, infrared spectroscopy, impedance spectroscopy and skin
blood flow measurements are discussed. After first presenting the basic pr
inciples of these methods, their application to the determination of SC bar
rier function and skin integrity is addressed, and the criteria for selecti
ng the most appropriate approach are considered.