title: Iontophoretic enhancement of timolol across human dermatomed skin in vitro.
abstract: The objective of this study was to assess the in vitro the iontophoretic delivery of Timolol across human dermatomed skin in order to determine whether therapeutic doses of this drug can be delivered. Anodal iontophoresis of Timolol was performed by manipulating the donor vehicle and the current density. It was observed that by reducing simultaneously the competitive ions (NaCl) from 8 to 4 g/l and the pH from 7.4 to 4.7, the iontophoretic flux was significantly increased by a factor of 1.5 (669+/-81 microg/cm h). In order to simulate the situation in a transdermal patch, the iontophoretic delivery of Timolol was also studied after adding an artificial porous membrane placed between the Timolol formulation and the human dermatomed skin. No significant difference was observed in the steady state flux across the skin when an artificial membrane was added. Furthermore, a linear relationship was found between current density and steady state flux. These results indicate that the iontophoretic delivery of Timolol can be accurately controlled by the applied current. Assuming a one to one in vitro/in vivo correlation the Timolol transport in vitro results in therapeutic plasma concentrations in humans with very low current densities limiting possible skin irritation.
authors.affiliation: Department of Pharmaceutical Technology, Leiden Amsterdam Center for Drug Research, P.O. Box RA 9502 2300 Leiden, The Netherlands. dfat@upatras.gr
authors.forename: Dimitrios G
authors.initials: DG
authors.lastname: Fatouros
authors.forename: Joke A
authors.initials: JA
authors.lastname: Bouwstra
mesh_terms: D000279:Administration, Cutaneous; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007477:Ions; D007478:Iontophoresis; D008567:Membranes, Artificial; D012869:Skin Absorption; D012965:Sodium Chloride / Q000737:chemistry; D013999:Timolol / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000319:Adrenergic beta-Antagonists; D007477:Ions; D008567:Membranes, Artificial; D012965:Sodium Chloride; D013999:Timolol