Correlation of transdermal iontophoretic phenylalanine and mannitol transport: test of the internal standard concept under DC iontophoresis and constant resistance AC iontophoresis conditions.

The purpose of this study was to test the feasibility of using an internal standard approach to predict the transdermal flux of phenylalanine (Phe) across human epidermal membrane (HEM) in vitro during iontophoresis of constant direct current (DC), constant skin resistance alternating current (AC) with DC offset (AC-plus-DC), symmetric constant resistance AC (AC-only), and constant current DC with the application of a polyelectrolyte. Under the constant current DC and AC-plus-DC conditions, a linear relationship between the permeation of Phe and that of mannitol was observed with a slope close to unity. The ratios of the Phe permeability coefficients to those of mannitol during iontophoresis with different HEM samples were essentially constant with significantly smaller inter-sample and intra-sample variabilities than those of the raw Phe permeability coefficient data. This demonstrates that mannitol is a good internal standard for predicting the transdermal iontophoretic flux of Phe under these two conditions. On the other hand, the correlations of the permeability coefficients of Phe and mannitol under the AC-only iontophoresis and iontophoresis with the polyelectrolyte are poorer than those observed during DC and AC-plus-DC iontophoresis. The poor correlations are believed to be related to Phe being a zwitterion and its anionic form in HEM. Previously, iontophoretic transport of glucose has been demonstrated to be essentially the same as that of mannitol. The good correlations between Phe and mannitol transport across HEM during DC and AC-plus-DC iontophoresis in the present study therefore suggest that glucose and its extraction can be used as the internal standard for iontophoretic Phe monitoring.