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微乳剂作为用于皮肤给药的胶体载体系统。第四部分:通过动态光散射研究基于利多卡因和丙胺卡因低共熔混合物作为胶体相的微乳剂系统。

Microemulsions as colloidal vehicle systems for dermal drug delivery. Part IV: Investigation of microemulsion systems based on a eutectic mixture of lidocaine and prilocaine as the colloidal phase by dynamic light scattering.

作者信息

Shukla Anuj, Krause Annett, Neubert Reinhard H H

机构信息

Department of Physics, Optics Group, Martin-Luther-University Halle-Wittenberg, 06099 Halle/Saale, Germany.

出版信息

J Pharm Pharmacol. 2003 Jun;55(6):741-8. doi: 10.1211/002235703765951339.

Abstract

Stable oil-in-water (o/w) microemulsions used as vehicles for dermal drug delivery have been developed using lidocaine (lignocaine) and prilocaine in oil form (eutectic mixture), a blend of a high (Tween 80, hydrophilic-lipophilic balance (HLB) = 15.0) and a low (Poloxamer 331, HLB = 1.0) HLB surfactant and propylene glycol-water as hydrophilic phase. These microemulsions were able to solubilize up to 20% eutectic mixture of lidocaine and prilocaine without phase separation. The dispersity of the oil phase was investigated by dynamic light scattering. Small colloidal droplets for stable microemulsions of 5~10 nm were observed. At constant surfactant and hydrophilic phase concentration, increasing the total drug concentration in the microemulsion resulted in an increase in the droplet size of the dispersed, colloidal phase. It was observed that a monolayer of surfactant surrounds the oil (eutectic mixture) core. Colloidal droplets of the microemulsion interact via hard sphere with supplementary attractive interaction. This observed interparticle attractive interaction could explain the observed phase behaviour with respect to change in the basicity of the hydrophilic phase as well as the increase in volume fraction of the dispersed, colloidal phase. It was also observed that the stability and size of this dispersed phase depends on the pH of the composition. Because these microemulsions formed stable, isotropic systems in the range of pH 9.5 to 10.4 with alkali buffer or NaOH solution instead of water as hydrophilic phase, so one can produce microemulsions in this pH area.

摘要

已开发出稳定的水包油(o/w)微乳剂用作皮肤给药载体,其使用油状利多卡因(盐酸利多卡因)和丙胺卡因(低共熔混合物)、高亲水性-亲脂性平衡(HLB)(吐温80,HLB = 15.0)和低HLB(泊洛沙姆331,HLB = 1.0)表面活性剂的混合物以及丙二醇-水作为亲水相。这些微乳剂能够溶解高达20%的利多卡因和丙胺卡因低共熔混合物而不发生相分离。通过动态光散射研究油相的分散性。观察到稳定微乳剂的小胶体液滴尺寸为5~10 nm。在表面活性剂和亲水相浓度恒定的情况下,增加微乳剂中总药物浓度会导致分散胶体相的液滴尺寸增大。观察到表面活性剂单层包围油(低共熔混合物)核。微乳剂的胶体液滴通过硬球相互作用并伴有额外的吸引相互作用。观察到的这种颗粒间吸引相互作用可以解释关于亲水相碱度变化以及分散胶体相体积分数增加所观察到的相行为。还观察到该分散相的稳定性和尺寸取决于组合物的pH值。由于这些微乳剂在pH 9.5至10.4范围内与碱性缓冲液或NaOH溶液而非水作为亲水相形成稳定的各向同性体系,因此可以在该pH区域制备微乳剂。

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