Enhanced iontophoretic delivery of buspirone hydrochloride across human skin using chemical enhancers.
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/cm(2), it was possible to achieve a BH steady state flux of approximately 350 microg/cm(2)h, which would be therapeutically effective if clinically duplicated. Importantly, 24 h of iontophoresis at 0.5 mA/cm(2) 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/cm(2)) iontophoresis was applied in conjunction with Azone treatment.
Meidan
Victor M
VM
Department of Physiology and Pharmacology, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.
Al-Khalili
Mohammad
M
Michniak
Bozena B
BB
D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000279:Administration, Cutaneous; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001381:Azepines / Q000494:pharmacology; D002065:Buspirone / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D000081005:Cyclohexane Monoterpenes; D003511:Cyclohexanols / Q000494:pharmacology; D053138:Cyclohexenes; D000077591:Eucalyptol; D006801:Humans; D066298:In Vitro Techniques; D007478:Iontophoresis; D008610:Menthol / Q000494:pharmacology; D039821:Monoterpenes / Q000494:pharmacology; D019301:Oleic Acid / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D012869:Skin Absorption / Q000187:drug effects*; D013997:Time Factors
D000277:Adjuvants, Pharmaceutic; D014151:Anti-Anxiety Agents; D001381:Azepines; D000081005:Cyclohexane Monoterpenes; D003511:Cyclohexanols; D053138:Cyclohexenes; D039821:Monoterpenes; D008610:Menthol; C035229:laurocapram; C016775:alpha-terpineol; D019301:Oleic Acid; C019466:menthone; D000077591:Eucalyptol; D002065:Buspirone