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