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In Vitro Optimization of Dexamethasone Phosphate Delivery by Iontophoresis

JP Sylvestre, PhD, is Postdoctoral Researcher, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, United Kingdom
RH Guy, PhD, is Professor, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, United Kingdom
MB Delgado-Charro, PhD, is Lecturer in Pharmaceutical Sciences, Department of Pharmacy and Pharmacology, University of Bath

Address all correspondence to Dr Guy at: r.h.guy{at}bath.ac.uk

Background and Purpose: This study was designed to evaluate the effects of competing ions and electroosmosis on the transdermal iontophoresis of dexamethasone phosphate (Dex-Phos) and to identify the optimal conditions for its delivery.

Methods: The experiments were performed using pig skin, in side-by-side diffusion cells (0.78 cm²), passing a constant current of 0.3 mA via Ag-AgCl electrodes. Dex-Phos transport was quantified for donor solutions (anodal and cathodal) containing different drug concentrations, with and without background electrolyte. Electrotransport of co-ion, citrate, and counterions Na⁺ and K⁺ also was quantified. The contribution of electroosmosis was evaluated by measuring the transport of the neutral marker (mannitol).

Results: Electromigration was the dominant mechanism of drug iontophoresis, and reduction in electroosmotic flow directed against the cathodic delivery of Dex-Phos did not improve drug delivery. The Dex-Phos flux from the cathode was found to be optimal (transport number of 0.012) when background electrolyte was excluded from the formulation. In this case, transport of the drug is limited principally by the competition with counterions (mainly Na⁺ with a transport number of 0.8) and the mobility of the drug in the membrane.

Discussion and Conclusion: Dex-Phos must be delivered from the cathode and formulated rationally, excluding mobile co-anions, to achieve optimal iontophoretic delivery.

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