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Enhanced iontophoretic delivery of buspirone hydrochloride across human skin using chemical enhancers

Meidan, V.M. and Al-Khalili, M. and Michniak, B.B. (2003) Enhanced iontophoretic delivery of buspirone hydrochloride across human skin using chemical enhancers. International Journal of Pharmaceutics, 264 (1-2). pp. 73-83. ISSN 0378-5173

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Abstract

Buspirone hydrochloride (BH) is a structurally and pharmacologically unique anxiolytic that is used to treat a variety of different anxiety conditions. The marketed product is named BuSpar®. The in vitro iontophoretic delivery of BH through human skin was investigated in order to evaluate the feasibility of delivering a therapeutic dose of BH by this route. We also examined the influence of co-formulations of chemical enhancers (Azone®, oleic acid, menthone, cineole, and terpineol) on BH permeation, both without iontophoresis and with iontophoresis—to look for possible synergistic effects. By applying iontophoresis at 0.5 mA/cm2, it was possible to achieve a BH steady state flux of approximately 350 μg/cm2 h, which would be therapeutically effective if clinically duplicated. Importantly, 24 h of iontophoresis at 0.5 mA/cm2 did not affect skin morphology and after the current was switched off, the skin’s permeability to BH rapidly reverted to its pre-iontophoretic level. Without iontophoreis, BH transdermal flux was significantly enhanced by the application of 2.5% (v/v) concentrations of Azone®, oleic acid, or menthone but not cineole or terpineol. Furthermore, this paper identified a synergistic transport enhancement effect developing when very low current (0.025 mA/cm2) iontophoresis was applied in conjuction with Azone® treatment.