Mechanistic study of alternating current iontophoresis and evaluation of internal standard in iontophoretic monitoring

The first topic of this dissertation is the study of the fundamental transport mechanisms of alternating current (AC) iontophoresis using a synthetic membrane system. AC frequencies ranging from 20 to 1000 Hz and AC fields ranging from 0.25 V/membrane to 0.5 V/membrane were investigated. A charged permeant, tetraethyl ammonium (TEA), and a neutral permeant, arabinose (ARA), were used in this study. The transport experiments showed that flux was enhanced by increasing the AC voltage and decreasing the AC frequency. Two theoretical transport models were developed: a homogeneous membrane model and a heterogeneous membrane model. Excellent agreement between model predictions and experimental data was observed when the data were compared to the simulations from the heterogeneous membrane model.; The second topic is the investigation of the effects of AC upon flux of neutral and ionic model permeants across human epidermal membrane (HEM) under two different conditions: constant AC voltage iontophoresis and constant HEM resistance with direct current (DC) offset iontophoresis. In the constant AC voltage study, it was demonstrated that AC could enhance the transport of the ionic permeant across HEM, but no enhancement was observed for the neutral permeant. In the constant HEM resistance study of AC with DC offset, linear relationships were observed between flux enhancement and the voltage of the direct current (DC) offset for both the neutral and ionic permeants. These results are consistent with the modified Nernst-Planck model.; The third topic was a study of an in-vitro test of the feasibility of using an internal standard approach to predict the transdermal flux of phenylalanine (Phe) across HEM during iontophoresis. 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 intersample and intrasample variabilities than those found with raw Phe permeability coefficient data. These results suggest that iontophoretic glucose extraction can be used as an internal standard for iontophoretic Phe monitoring.