Effect of lipophilicity on in vivo iontophoretic delivery. I. NSAIDs.

The effect of drug lipophilicity on in vivo iontophoretic transdermal absorption was evaluated. Non-steroidal anti-inflammatory drugs (NSAIDs) were selected as model drugs with a wide range of lipophilicity: salicylic acid (SA), ketoprofen (KP), naproxen (NP) and indomethacin (IM). Cathodal iontophoresis of NSAIDs was conducted in rats (0.625 mA/cm2; 90 min), and drug concentrations in skin, cutaneous vein and systemic vein were determined. Skin concentrations of NSAID were higher in the case of lipophilic drugs (SA=KP=NP<IM), whereas cutaneous plasma concentrations decreased with an increase in lipophilicity (SA>KP=NP>IM). Additionally, the dependence of drug lipophilicity on systemic plasma concentration was similar to cutaneous plasma concentration. The transfer rate from skin to cutaneous vein (R(SC)) was calculated from the arterio-venous plasma concentration difference of drug in the skin. Normalized R(SC) by skin concentration (R(SC)/X(S)) yielded a negative correlation with the logarithm of n-octanol/buffer partition coefficient (Log P at pH 7.4), suggesting that transfer of NSAIDs from skin to cutaneous vein decreased with increasing lipophilicity (SA>KP=NP>IM). This correlation means that drug partitioning between stratum corneum and viable epidermis might be a dominant step.