UNIGE document Scientific Article
previous document  unige:22914  next document
add to browser collection
Title

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

Authors
Ganem-Rondero, Adriana
Quintanar-Guerrero, David
López-Castellano, Alicia C
Merino, Virginia
Published in European Journal of Pharmaceutical Sciences. 2010, vol. 39, no. 5, p. 387-93
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, CutaneousAnimalsAntiemetics/administration & dosage/pharmacokineticsArea Under CurveChromatography, High Pressure LiquidGranisetron/administration & dosage/pharmacokineticsHalf-LifeIontophoresis/methodsLimit of DetectionMaleRatsRats, WistarSerotonin Antagonists/administration & dosage/pharmacokineticsSkin/metabolismSwine
Identifiers
PMID: 20096354
Full text
Article (Author postprint) (527 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Structures
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. 387-93. https://archive-ouverte.unige.ch/unige:22914

147 hits

0 download

Update

Deposited on : 2012-09-17

Export document
Format :
Citation style :