Abstract
Purpose. To delineate the contributions of electrorepulsion and electroosmosis to the iontophoretic flux of 5-FU across porcine skin in vitro. Also, the isoelectric point (pI) of the skin model was determined.
Methods. The electrotransport of 5-FU, anode-to-cathode ('anodal') and cathode-to-anode ('cathodal') was determined as a function of the pH of the electrolyte bathing the skin.
Results. At pH 8.5, the drug (pKa ∼8) is negatively charged and 'cathodal', viz. electrorepulsive, transport is much greater than that in the opposite direction. At pH 7.4, where ∼25% of 5-FU is charged, electrorepulsive and electroosmotic ('anodal') fluxes are balanced. Decreasing the pH to 6, and then 5, reduces the percentage of ionized 5-FU such that 'anodal' electroosmosis dominates across the negatively-charged membrane. But, at pH 4, 'anodal' and 'cathodal' fluxes are again equal suggesting neutralization of the skin (i.e., pI ∼ 4). This is confirmed at pH 3, where 'cathodal' electroosmosis dominates across the now net-positively charged barrier.
Conclusions. Electrotransport is sensitive, mechanistically, to the properties of the permeant and of the skin; interactions of, for example, the drug or constituents of a formulation, that alter the barrier's net charge, can affect iontophoretic delivery. The pI of porcine ear skin is ∼4.
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Merino, V., López, A., Kalia, Y.N. et al. Electrorepulsion Versus Electroosmosis: Effect of pH on the lontophoretic Flux of 5-Fluorouracil. Pharm Res 16, 758–761 (1999). https://doi.org/10.1023/A:1018841111922
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DOI: https://doi.org/10.1023/A:1018841111922