en
Scientific article
English

Using transdermal iontophoresis to increase granisetron delivery across skin in vitro and in vivo: effect of experimental conditions and a comparison with other enhancement strategies

Published inEuropean journal of pharmaceutical sciences, vol. 39, no. 5, p. 387-393
Publication date2010
Abstract

The objectives of the study were (i) to investigate the effect of experimental parameters on the iontophoretic transport of granisetron, (ii) to identify the relative contributions of electromigration (EM) and electroosmosis (EO), (iii) to determine the feasibility of delivering therapeutic amounts of drug for the treatment of chemotherapy-induced nausea and vomiting and (iv) to test the in vitro results in a simple animal model in vivo. Preliminary in vitro studies using aqueous granisetron formulations investigating the effect of drug concentration (5, 10, 20 and 40 mM) and current density (0.1, 0.2, 0.3 mA cm(-2)) were performed using porcine ear skin. As expected, cumulative delivery in vitro at the 20 and 40 mM concentrations was significantly greater than that at 5 and 10mM, which were not statistically different (p<0.05). Increasing the applied current density from 0.1 to 0.3 mA cm(-2) resulted in a approximately 4.2-fold increase in iontophoretic flux. Furthermore, in the absence of Na(+) in the formulation, no dependence of iontophoretic flux on drug concentration was reported (at a granisetron concentration of 40 mM, the transport rate was 2.93+/-0.62 microg cm(-2)min(-1)). Co-iontophoresis of acetaminophen was used to show that EM was the predominant transport mechanism accounting for 71-86% of total granisetron delivery. In vivo studies in Wistar rats (40 mM granisetron; application of 0.3 mA cm(-2) for 5h with Ag/AgCl electrodes and salt bridges) showed an average iontophoretic input rate (k(input)) of 0.83+/-0.26 microg min(-1) and a maximum plasma concentration (C(max)) of 0.092+/-0.004 microg ml(-1). Based on these results and given the known pharmacokinetics, transdermal iontophoresis could achieve therapeutic drug levels for the management of chemotherapy-induced emesis using a reasonably sized (4-6 cm(2)) patch.

Keywords
  • Administration, Cutaneous
  • Animals
  • Antiemetics/administration & dosage/pharmacokinetics
  • Area Under Curve
  • Chromatography, High Pressure Liquid
  • Granisetron/administration & dosage/pharmacokinetics
  • Half-Life
  • Iontophoresis/methods
  • Limit of Detection
  • Male
  • Rats
  • Rats, Wistar
  • Serotonin Antagonists/administration & dosage/pharmacokinetics
  • Skin/metabolism
  • Swine
Citation (ISO format)
CAZARES DELGADILLO, Jennyfer et al. Using transdermal iontophoresis to increase granisetron delivery across skin in vitro and in vivo: effect of experimental conditions and a comparison with other enhancement strategies. In: European journal of pharmaceutical sciences, 2010, vol. 39, n° 5, p. 387–393. doi: 10.1016/j.ejps.2010.01.008
Main files (1)
Article (Accepted version)
accessLevelRestricted
Identifiers
ISSN of the journal0928-0987
501views
0downloads

Technical informations

Creation09/03/2012 1:36:00 PM
First validation09/03/2012 1:36:00 PM
Update time03/14/2023 5:40:52 PM
Status update03/14/2023 5:40:51 PM
Last indexation01/16/2024 12:13:59 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack