title: A novel electronic skin patch for delivery and pharmacokinetic evaluation of donepezil following transdermal iontophoresis.
abstract: The nature of Alzheimer's disease limits the effectiveness of available oral treatments. The aim of this study was to assess the feasibility of transdermal iontophoretic delivery of donepezil in a hairless rat model as a potential treatment modality in Alzheimer's and to evaluate the effect of current densities on its pharmacokinetics. Donepezil loaded integrated Wearable Electronic Drug Delivery (WEDD(®)) patches supplied current levels of 0, 0.13, 0.26 and 0.39 mA. Plasma extracted donepezil was analyzed by HPLC. Noncompartmental analysis was used to characterize disposition of the drug. The amount delivered across hairless rat skin and areas under the curve (AUC) were found to rise in proportion to the current levels. Peak plasma levels of 0.094, 0.237 and 0.336 μg/ml were achieved at 0.13, 0.26 and 0.39 mA respectively. Time to peak plasma concentrations was after termination of current and same for all current levels. Transdermal elimination half-life was significantly increased from the true value of 3.2h due to depot formation, prolonging complete absorption of the drug. Donepezil was successfully delivered iontophoretically at levels sufficient to produce pharmacodymanic effect. Pharmacokinetic analysis demonstrated linear kinetics at the current levels used and flip flop kinetics following iontophoretic administration.
authors.affiliation: Transdermal Delivery Laboratory, College of Pharmacy and Health Sciences, Mercer University, Atlanta, GA 30341-4155, USA.
authors.forename: Sonal
authors.initials: S
authors.lastname: Saluja
authors.forename: Purna C
authors.initials: PC
authors.lastname: Kasha
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Paturi
authors.forename: Carter
authors.initials: C
authors.lastname: Anderson
authors.forename: Russell
authors.initials: R
authors.lastname: Morris
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Banga
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D004008:Diclofenac / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D055615:Electrical Equipment and Supplies; D007478:Iontophoresis; D051381:Rats; D054772:Rats, Hairless; D012867:Skin / Q000378:metabolism; D057968:Transdermal Patch
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac
keywords: Alzheimers; Donepezil; Electronic patches; Iontophoresis; Transdermal