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KMID : 0369820100400020091
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Jorunal of Korean Pharmaceutical Sciences
2010 Volume.40 No. 2 p.91 ~ p.100
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Electrotransport of Donepezil Hydrochloride from Poly(ethylene oxide) Hydrogel
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Choi Yu-Ri
Oh Seaung-Youl
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Abstract
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The objective of this work is to study transdermal delivery of donepezil hydrochloride (DH) using iontophoresis and to evaluate various factors which affect the transdermal transport. After the flux study using 4 kinds of hydrogel, hydrogel containing 8% poly(ethylene oxide) (PEO) was chosen as the hydrogel for further studies. Under experimental condition, DH was stable. We have studied the effect of polarity, current density, drug concentration and current profile on transdermal flux and compared the results. In vitro flux study was performed at , using side-by-side diffusion cell and full thickness hairless mouse skin. DH is positively charged at pH 7.4, and anodal delivery was much larger than cathodal and passive delivery at all current densities studied (0.2, 0.4 and 0.6 mA/). Cathodal delivery showed higher flux than passive flux. Flux increased as the concentration of DH in hydrogel increased. Pulsatile application of current showed smaller flux value than the application of continuous current. Based on these results, we have evaluated the possibility of delivering enough amount of DH to reach the therapeutic level. The maximum cumulative amount of DH transported for 12 hours was 455 when the amount of DH in the hydrogel was 3 mg/mL and the current density was 0.4 mA/. If the patch size is 10 , then we can deliver 4.6 mg for 12 hours. Because the daily dosage of DH is 5 mg, it seems possible to deliver clinically effective amount of DH using iontophoresis. This study also provides some information about the role of electrorepulsion and electroosmosis during the transport through skin.
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KEYWORD
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Iontophoresis, donepezil hydrochloride, hydrogel, Alzheimer’s disease, electrorepulsion
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