Ion-exchange membrane assisted transdermal iontophoretic delivery of salicylate and acyclovir

Abstract

The presence of endogenous competing counterions is a main reason for the generally low efficiency of transdermal iontophoretic drug delivery. The objective of the present study was to test the hypothesis that the incorporation of an ion-exchange membrane (Ionac) in an iontophoresis system to hinder transdermal transport of these counterions can enhance iontophoretic delivery. The properties of Ionac were characterized in passive and iontophoretic transport experiments. Iontophoretic transport across human epidermal membrane (HEM) and across HEM in series with Ionac was then studied. To assess the effect of HEM electrical resistance upon Ionac-assisted iontophoresis, HEM resistance was reduced in the iontophoresis experiments with alternating current (AC). Salicylate (SA) was the negatively charged permeant first tested in this study. Mannitol was the model permeant to examine the effects of electroosmosis. At the completion of the SA study, experiments were performed with acyclovir (ACV), an antiviral drug with limited water solubility. When Ionac was used to enhance SA transdermal fluxes, higher SA .uxes were observed with HEM of lower resistances in Ionac-assisted iontophoresis. Up to a four-fold flux enhancement was achieved when the electrical resistance of HEM was reduced using an AC iontophoresis method. For ACV, two-fold flux enhancement was observed in Ionac-assisted iontophoresis compared with the conventional iontophoresis baseline. In all experiments, the contribution of electroosmosis to drug transport was less than 10%. The present study has demonstrated the potential of a new approach using a positively charged ion-exchange membrane to enhance transdermal iontophoretic transport of negatively charged drugs.

Transepidermal water loss and skin conductance as barrier integrity tests

“…In these experiments, the skin is maintained between the donor and receptor diffusion chambers, and the permeation of a chemical from the donor chamber into and across the skin is measured. These skin permeation studies provide valuable information in risk assessment related to percutaneous absorption after skin exposure to hazardous chemicals (Flynn, 1990; Frasch et al, 2014), development of topical and transdermal formulations (Nicoli et al, 2006; Roy et al, 1996), evaluation and comparison of dermatological products (Bassani and Banov, 2016; Olivier et al, 2003), assessment of new topical and transdermal drug delivery technologies (Li et al, 2001; Tezel et al, 2004; Xu et al, 2009), and identification of the mechanisms of skin formulations such as permeation enhancers (Chantasart and Li, 2012; Charoenputtakun et al, 2015). These studies can also be used for quality control in product manufacturing (USP725, 2009) and bioequivalence assessment (FDA, 2016; Franz et al, 2009; Lehman and Franz, 2014).…”

Effect of lipopeptides and iontophoresis on aciclovir skin delivery

“…Iontophoresis is a well known technique used to increase transdermal drug delivery and skin retention [22,27–29] . Even if at pH 7.4 aciclovir existed almost completely in its unionized form, different authors have demonstrated the usefulness of this technique due to the electroosmotic mechanism (at pH 7.4 the electroosmotic flow was in the anode‐to‐cathode direction.)…”

Effects of alternating current frequency and permeation enhancers upon human epidermal membrane

“…Transdermal iontophoretic drug delivery typically has low transport efficiency. A previous study (Xu et al, in press) has shown that the incorporation of an ion exchange membrane having a charge opposite to that of the drug ion in an iontophoresis system can enhance transdermal iontophoretic transport (i.e., permeant transference number) by approximately 2 to 4 times when the electrical resistance of HEM was lowered to and maintained at 0.5 kΩ with AC. To optimize AC in this application, the interplay of AC frequency, AC voltage, and the extent of pore induction in HEM under AC should be understood.…”