Transdermal therapeutic systems for memantine delivery. Comparison of passive and iontophoretic transport

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• 作者：S. del Rí ; o-Sancho^a ; ^b ; ^{sergiodelrio@hotmail.es} ; C.E. Serna-Jimé ; nez^a ; M. Sebastiá ; n-Morelló ; ^a ; M.A. Calatayud-Pascual^a ; C. Balaguer-Ferná ; ndez^a ; A. Femení ; a-Font^a ; Y.N. Kalia^b ; V. Merino^c ; A. Ló ; pez-Castellano^a
• 关键词：Memantine ; Transdermal delivery ; Occlusive-systems ; Chemical penetration enhancers ; Iontophoresis
• 刊名：International Journal of Pharmaceutics
• 出版年：2017
• 出版时间：30 January 2017
• 年：2017
• 卷：517
• 期：1-2
• 页码：104-111
• 全文大小：888 K
• 卷排序：517

文摘

Memantine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist used in the treatment of moderate to severe dementia including the symptoms of Alzheimer’s disease (AD). It is administered orally but compliance, swallowing problems and the routine use of multiple medications in elderly AD patients means that an alternative route of administration would be of interest.The aim of the present study was to develop memantine hydrochloride occlusive transdermal therapeutic systems (TTS) for passive and iontophoretic delivery across the skin. Polyvinyl pyrrolidone (PVP) and a mixture with polyvinyl alcohol (PVA) were employed as polymeric matrices. The study involved the TTS characterization in addition to quantification of the memantine transport across porcine skin in vitro.The evaluation of the TTS physical properties suggested that systems were made more mechanically resistant by including PVA (6%) or high concentrations of PVP (24%). Moreover, a linear correlation was observed between the concentration of PVP and the bioadhesion of the systems. Drug delivery experiments showed that the highest transdermal flux provided by a passive TTS (PVP 24% w/w limonene) was 8.89 ± 0.81 μg cm−2 h−1 whereas the highest iontophoretic transport was 46.4 ± 3.6 μg cm−2 h−1. These innovative TTS would enable two dosage regimens that could lead to therapeutic plasma concentrations.