Iontophoresis of dexamethasone phosphate: competition with chloride ions.
The objective was to study the competition of chloride released from a Ag/AgCl cathode on the iontophoretic delivery of dexamethasone phosphate (Dex-Phos). Iontophoresis of Dex-Phos was performed in side-by-side diffusion cells (0.78 cm(2)) using pig skin. A 0.3 mA constant current was applied via Ag/AgCl electrodes. The amounts of Dex-Phos and dexamethasone (Dex) were also quantified in the stratum corneum (SC), using tape-stripping, after passive and iontophoretic delivery. The profiles of Dex-Phos and Dex, as a function of position in the SC, were deduced. The iontophoretic delivery of Dex-Phos from pure water was unaffected by the accumulation of Cl- released by the donor cathode when the drug's concentration was 4.25 mM to 17 mM. At 0.85 mM, however, Cl- competition was significant and the drug flux was significantly reduced. Formulation of the drug in the presence of Cl- resulted in a non-linear dependence of flux on the molar fraction of the drug. Tape-stripping experiments confirmed the enhanced delivery of Dex-Phos by iontophoresis relative to passive diffusion, with Dex-Phos concentration greater inside the barrier post-iontophoresis than that in the donor. The latter observation could explain the robustness of Dex-Phos delivery to the presence of Cl- in the donor solution.
Sylvestre
J-P
JP
Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath BA27AY, UK.
Díaz-Marín
C
C
Delgado-Charro
M B
MB
Guy
R H
RH
D000279:Administration, Cutaneous; D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D007478:Iontophoresis / Q000379:methods*; D012869:Skin Absorption; D012965:Sodium Chloride / Q000378:metabolism; D013552:Swine
D002712:Chlorides; C004180:dexamethasone 21-phosphate; D012965:Sodium Chloride; D003907:Dexamethasone