Pharmacokinetics, Pharmacodynamics and Drug Metabolism
Transdermal Delivery Using a Novel Electrochemical Device, Part 2: In Vivo Study in Humans

https://doi.org/10.1002/jps.23108Get rights and content

ABSTRACT

A single-center, open-label, and dose-escalation clinical trial has been performed using a novel electrochemical transdermal patch comprising a drug-loaded hydrogel sandwiched between two silver electrodes. The lower electrode is attached flatly to skin via an adhesive layer. This noniontophoretic device produces flux enhancement via voltage-induced electrolysis of the water in the hydrogel. A voltage application of 2 V over 60 s produced release of approximately 315 to 340 μg of fentanyl from a patch. A single-voltage application at t = 16 h produced a maximum plasma level of approximately 200 pg/mL before patch removal at t = 41 h. Consecutive voltage applications at t = 16 h and t = 40 h produced a maximum plasma level of approximately 730 pg/mL. The lag time between voltage application and achievement of a plasma profile plateau is longer than that reported for an iontophoretic patch. The patch's advantage is production of an on-demand plasma profile without the use of potentially irritating iontophoresis. In contrast to a passive transdermal system, it is possible to adjust the plasma profile by using voltage application. It is not necessary to apply a continual current, in contrast to iontophoretic systems. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:2262–2268, 2012

Section snippets

INTRODUCTION

In our first publication,1 we elucidated the mechanism of working of a novel electrochemical transdermal patch comprising a drug-loaded hydrogel sandwiched between two silver electrodes. The lower electrode is attached flatly to skin via a layer of pressure-sensitive adhesive, whereas the upper electrode has no skin contact. Application of voltage, for example, 2 V, over a period of 60 s to the device resulted in sufficient release of fentanyl to give a measured flux through a contiguous,

Electrochemical Patches

The electrochemical transdermal patch for fentanyl has been described fully before.1 Briefly, it comprises a hydrogel reservoir containing 1.57% fentanyl citrate sandwiched between two Ag electrodes attached to a voltage source. The use of Ag electrodes is essential for correct working of the patch.1 In the presence of chloride in the gel the oxidation at the anode causes formation of sparingly soluble silver chloride and does not release H3O+. The latter would hinder increase in pH of the

Treatment Groups A1–2 (Single-Voltage Application)

Figure 1 shows the fentanyl plasma profiles of concentration, cp(t), versus time, t, for the two subjects each carrying a single-electrochemical patch receiving a single-voltage application of 2.5 V for 60 s at t = 16 h (Group A1). Up to the point of voltage application, there is no quantifiable plasma profile with either subject. In vitro studies of fentanyl release/permeation from the electrochemical patch through excised nude mouse skin prior to voltage application showed low fluxes of 2 μg/(cm2

CONCLUSIONS

The results demonstrate that the electrochemical patch can be used to produce on-demand plasma concentrations of fentanyl at a therapeutically effective level. The interindividual variation in cpmax and AUC is, however, large and is attributed to fentanyl's variable skin absorption and global elimination kinetics. The electrochemical patch's advantages are that it is possible to adjust the plasma profile by using voltage application and it is not necessary to apply a continual current, in

REFERENCES (23)

  • G. Sathayn et al.

    Passive absorption of fentanyl from the fentanyl HCl iontophoretic transdermal system

    Curr Med Res Opin

    (2009)
  • Cited by (0)

    View full text