A novel electronic skin patch for delivery and pharmacokinetic evaluation of donepezil following transdermal iontophoresis

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 effec...

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Bibliographic Details
Published in:International journal of pharmaceutics 2013-09, Vol.453 (2), p.395-399
Main Authors: Saluja, Sonal, Kasha, Purna C., Paturi, Jyotsna, Anderson, Carter, Morris, Russell, Banga, Ajay K.
Format: Article
Language:English
Subjects:
Alzheimer disease
Alzheimers
animal models
Animals
Anti-Inflammatory Agents, Non-Steroidal - administration & dosage
Anti-Inflammatory Agents, Non-Steroidal - blood
Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics
Diclofenac - administration & dosage
Diclofenac - blood
Diclofenac - pharmacokinetics
Donepezil
drugs
Electrical Equipment and Supplies
Electronic patches
half life
high performance liquid chromatography
Iontophoresis
pharmacokinetics
Rats
Rats, Hairless
Skin - metabolism
Transdermal
Transdermal Patch
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Summary: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 0.39mA. 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 0.336μg/ml were achieved at 0.13, 0.26 and 0.39mA 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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2013.05.029