NMR characterisation and transdermal drug delivery potential of microemulsion systems
NMR characterisation and transdermal drug delivery potential of microemulsion systems
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DOI：
10.1016/s0168-3659(00)00325-4
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发表时间：
2000-12-03
影响因子：
10.8
通讯作者：
Jaroszewski, JW
中科院分区：
文献类型：
--
作者：
Kreilgaard, M;Pedersen, EJ;Jaroszewski, JW
本研究的目的是研究微乳（Labrasol/ Plurol Isostearique/异硬脂酸异硬脂酸酯/水）的结构和组成对其亲脂性（利多卡因）和亲水性模型药物（盐酸丙胺卡因）的经皮给药潜力的影响，并比较微乳与传统载体的药物给药潜力。自扩散系数由脉冲梯度自旋回波核磁共振谱和T-1弛豫时间测定用于分散的微乳液。采用Franz型扩散池测定了利多卡因和盐酸丙胺卡因的体外透皮速率。制剂成分能够形成多种微乳液组合物，其范围从水连续到油连续聚集体，可能的双连续结构，对于亲脂性和亲水性化合物具有优异的溶解性。与传统的水包油乳剂相比，微乳剂使利多卡因的经皮通量增加了4倍，而与水凝胶相比，盐酸丙胺卡因的经皮通量增加了近10倍。载剂中药物的自扩散与透皮通量之间存在相关性。发现微乳液制剂的经皮给药增加主要是由于药物的溶解度增加，并且似乎取决于单个载体中的药物流动性。微乳液不干扰皮肤屏障，表明皮肤刺激性低。(C)2000 Elsevier Science B. V.保留所有权利。
The purpose of this study was to investigate the influence of structure and composition of microemulsions (Labrasol/ Plurol Isostearique/isostearylic isostearate/water) on their transdermal delivery potential of a lipophilic (lidocaine) and a hydrophilic model drug (prilocaine hydrochloride), and to compare the drug delivery potential of microemulsions to conventional vehicles. Self-diffusion coefficients determined by pulsed-gradient spin-echo NMR spectroscopy and T-1 relaxation times were used to characterise the microemulsions. Transdermal flux of lidocaine and prilocaine hydrochloride through rat skin was determined in vitro using Franz-type diffusion cells. The formulation constituents enabled a broad variety of microemulsion compositions, which ranged from water-continuous to oil-continuous aggregates over possible bicontinuous structures, with excellent solubility properties for both lipophilic and hydrophilic compounds. The microemulsions increased transdermal flux of lidocaine up to four times compared to a conventional oil-in-water emulsion, and that of prilocaine hydrochloride almost 10 times compared to a hydrogel. A correlation between self-diffusion of the drugs in the vehicles and transdermal flux was indicated. The increased transdermal drug delivery from microemulsion formulations was found to be due mainly to the increased solubility of drugs and appeared to be dependent on the drug mobility in the individual vehicle. The microemulsions did not perturb the skin barrier, indicating a low skin irritancy. (C) 2000 Elsevier Science B.V. All rights reserved.