In vivo transdermal delivery of diclofenac by ion-exchange iontophoresis with geraniol.

A novel iontophoretic system utilizing ion-exchange membranes is effective for selective transdermal delivery of ionized drugs. In the present study, we examined in vivo availability and safety of ion-exchange iontophoresis in the transdermal delivery of anionic diclofenac, a well known anti-inflammatory medication, to rat dorsal skin. While iontophoresis increased the plasma concentration of diclofenac sodium and skin injury was not observed, no anti-inflammatory effect was exerted. To enhance the efficiency of transdermal delivery of diclofenac sodium, iontophoresis was combined with topical application of one of three terpenes (menthol, nerolidol or geraniol) as chemical enhancers. By combining iontophoresis with geraniol, the plasma concentration of diclofenac sodium increased over 20-fold, and suppression of inflammation was achieved. Skin irritation was not seen even after 1.5 h iontophoresis. The enhancing effect of geraniol is attributed to increased penetration of the drug into the stratum corneum as well as enhanced transport across the anion-exchange membrane. Ion-exchange iontophoresis combined with geraniol is a highly effective transdermal delivery system.