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1.
Int J Pharm ; 453(2): 395-9, 2013 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-23735902

RESUMO

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.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Diclofenaco/administração & dosagem , Equipamentos e Provisões Elétricas , Adesivo Transdérmico , Animais , Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/farmacocinética , Diclofenaco/sangue , Diclofenaco/farmacocinética , Iontoforese , Ratos , Ratos Pelados , Pele/metabolismo
2.
J Drug Target ; 18(2): 134-40, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19772394

RESUMO

In this study, the effect of iontophoresis on the transdermal and intradermal delivery of dexamethasone sodium phosphate (DEX-P) was examined in vitro and in vivo in the hairless rat model by skin permeation studies, tape stripping, and skin extraction. Cathodal or anodal iontophoresis (ITP) was performed and samples were analyzed by HPLC. In vitro experiments revealed that cathodal ITP significantly enhanced the cumulative amount of DEX-P permeating through the skin when compared to passive and anodal delivery. Tape stripping and skin extraction studies performed in vivo after ITP showed enhanced deposition of the drug in the stratum corneum and underlying skin when compared to passive delivery. The DEX-P and DEX depot formed in the stratum corneum and underlying skin were retained for at least 48 h and 24 h, respectively. In conclusion, ITP demonstrated potential as a feasible enhancement technique to drive the drug into and through the skin in significant amounts as compared to passive delivery.


Assuntos
Dexametasona/análogos & derivados , Glucocorticoides/administração & dosagem , Glucocorticoides/farmacocinética , Pele/metabolismo , Administração Cutânea , Animais , Dexametasona/administração & dosagem , Dexametasona/química , Dexametasona/farmacocinética , Injeções Intradérmicas , Iontoforese , Masculino , Estrutura Molecular , Permeabilidade , Ratos , Ratos Pelados , Absorção Cutânea
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