Scientific article

Transdermal iontophoresis of dexamethasone sodium phosphate in vitro and in vivo: effect of experimental parameters and skin type on drug stability and transport kinetics

Published inEuropean journal of pharmaceutics and biopharmaceutics, vol. 75, no. 2, p. 173-178
Publication date2010

The aim of this study was to investigate the cathodal iontophoresis of dexamethasone sodium phosphate (DEX-P) in vitro and in vivo and to determine the feasibility of delivering therapeutic amounts of the drug for the treatment of chemotherapy-induced emesis. Stability studies, performed to investigate the susceptibility of the phosphate ester linkage to hydrolysis, confirmed that conversion of DEX-P to dexamethasone (DEX) upon exposure to samples of human, porcine and rat dermis for 7 h was limited (82.2+/-0.4%, 72.5+/-4.8% and 78.6+/-6.0% remained intact) and did not point to any major inter-species differences. Iontophoretic transport of DEX-P across dermatomed porcine skin (0.75 mm thickness) was studied in vitro as a function of concentration (10, 20, 40 mM) and current density (0.1, 0.3, 0.5 mA cm(-2)) using flow-through diffusion cells. Increasing concentration of DEX-P from 10 to 40 mM resulted in a approximately 4-fold increase in cumulative permeation (35.65+/-23.20 and 137.90+/-53.90 microg cm(-2), respectively). Good linearity was also observed between DEX-P flux and the applied current density (i(d); 0.1, 0.3, 0.5 mA cm(-2); J(DEX) (microg cm(2) h(-1))=237.98 i(d)-21.32, r(2)=0.96). Moreover, separation of the DEX-P formulation from the cathode compartment by means of a salt bridge - hence removing competition from Cl(-) ions generated at the cathode - produced a 2-fold increase in steady-state iontophoretic flux (40 mM, 0.3 mA cm(-2); 20.98+/-7.96 and 41.82+/-11.98 microg cm(-2) h(-1), respectively). Pharmacokinetic parameters were determined in Wistar rats (40 mM DEX-P; 0.5 mA cm(-2) for 5h with Ag/AgCl electrodes and salt bridges). Results showed that DEX-P was almost completely converted to DEX in the bloodstream, and significant DEX levels were achieved rapidly. The flux across rat skin in vivo (1.66+/-0.20 microg cm(-2) min(-1)), calculated from the input rate, was not statistically different from the flux obtained in vitro across dermatomed porcine skin (1.79+/-0.49 microg cm(-2) min(-1)). The results suggest that DEX-P delivery rates would be sufficient for the management of chemotherapy-induced emesis.

  • Administration, Cutaneous
  • Animals
  • Antineoplastic Agents/adverse effects
  • Dexamethasone/administration & dosage/analogs & derivatives/pharmacokinetics
  • Dose-Response Relationship, Drug
  • Drug Stability
  • Glucocorticoids/administration & dosage/pharmacokinetics
  • Humans
  • Hydrolysis
  • Iontophoresis
  • Male
  • Rats
  • Rats, Wistar
  • Skin/metabolism
  • Skin Absorption
  • Species Specificity
  • Swine
  • Time Factors
  • Vomiting/chemically induced/prevention & control
Citation (ISO format)
CAZARES DELGADILLO, Jennyfer et al. Transdermal iontophoresis of dexamethasone sodium phosphate in vitro and in vivo: effect of experimental parameters and skin type on drug stability and transport kinetics. In: European journal of pharmaceutics and biopharmaceutics, 2010, vol. 75, n° 2, p. 173–178. doi: 10.1016/j.ejpb.2010.03.011
Main files (1)
Article (Accepted version)
ISSN of the journal0939-6411

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First validation08/29/2012 2:20:00 PM
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