Passive and iontophoretic delivery of three diclofenac salts across various skin types

The in vitro permeation of three diclofenac salts--diclofenac sodium (DFS), diclofenac potassium (DFP) and diclofenac diethylammonium (DFD)-across skin by both passive and iontophoretic transport were investigated. Various skin types were used as the barriers to elucidate the mechanism controlling transdermal delivery of diclofenac salts. The importance of the intercellular (paracellular) route for both DFS and DFP in passive permeation was elucidated. The transfollicular route constitutes an important permeation pathway for DFS but not for DFP. The route and mechanism for transdermal iontophoresis of DFD across the skin was somewhat different to that of the other salts. Hair follicles may be a more important pathway for DFD than for DFS and DFP under iontophoresis, while the intercellular lipid pathway showed the opposite result. Combination of iontophoresis and a penetration enhancer, cardamom oil, did not show a synergistic effect on diclofenac salt permeation. The results of this investigation suggest that the transdermal mechanism and the route of diclofenac salt uptake via passive and iontophoretic transport can be affected by their counterions.