REVERSE IONTOPHORESIS - PARAMETERS DETERMINING ELECTROOSMOTIC FLOW .1. PH AND IONIC-STRENGTH

It has been previously demonstrated that electroosmosis (the convectiv e movement of solvent that occurs through a charged 'pore' in response to the preferential passage of counter-ions when an electric field is applied) can be used in 'reverse iontophoresis', where the imposition of an electric current across the skin is used to extract a substance of interest (e.g., glucose) from within or beneath the tissue to the surface of the body. The goal of the research reported here was to exa mine parameters which determine electroosmosis, such that the convecti ve flow of solvent across the skin during iontophoresis may be maximiz ed, and the sensitivity and precision of the procedure optimized. Usin g mannitol as an appropriate marker molecule, therefore, electroosmoti c flow during reverse iontophoresis has been examined as a function of the pH and ionic strength of the electrolyte solutions contained with in the electrode compartments located on the skin surface. The impact of using a limited set of different current waveforms was also studied . As expected from the permselectivity of the skin, extraction to the cathode was preferred over that to the anode at pH 7.4. Cathodal extra ction was enhanced by increasing the pH of the surface electrolyte con versely, electroosmosis to the anode was improved by lowering the pH ( due, presumably, to neutralization of the net negative charge on the i on-conducting pathways through the skin). Reducing the electrolyte ion ic strength in the electrode chambers (relative to the physiological l evel present beneath the tissue) enhanced both cathodal (in particular ) and anodal extraction; a minimum quantity of electrolyte, however, m ust be present in order to sustain the necessary electrochemistry of t he iontophoretic system. Finally, neither periodic interruption of cur rent flow, nor periodic alternation of electrode polarity (strategies which have been proposed to limit the acute irritation induced by cons tant current iontophoresis, i.e., allowing the skin an opportunity to 'depolarize') adversely affected the overall efficiency of the extract ion process.