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阳离子表面活性剂对表面活性和非表面活性模型药物在三相系统中的转运及乳液稳定性的影响。

Effect of cationic surfactant on transport of surface-active and non-surface-active model drugs and emulsion stability in triphasic systems.

作者信息

Chidambaram N, Burgess D J

机构信息

Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut, 06269, USA.

出版信息

AAPS PharmSci. 2000;2(3):E28.

Abstract

A study was carried out to determine the effect of excess surfactant on transport kinetics in emulsions, using surface-active (phenobarbital, barbital) and non-surface-active (phenylazoaniline, benzocaine) model drugs (pH 7.0). Mineral oil was chosen as the oil phase, and the ionic surfactant cetyltrimethylammonium bromide (CTAB) was chosen as the emulsifier. The effect of nonionic surfactant Brij 97 on transport kinetics of these model drugs were determined by authors elsewhere. Model drug transport in the triphasic systems was investigated using side-by-side diffusion cells mounted with hydrophilic dialysis membranes (molecular weight cutoffs 1 kD and 50 kD) and a novel bulk equilibrium reverse dialysis bag technique. Emulsion stability was determined by droplet size analysis as a function of time, temperature, and the presence of model drugs using photon correlation spectroscopy. Mineral oil/water partition coefficients and aqueous solubilities were determined in the presence of surfactant. The droplet size of the CTAB-stabilized emulsion system is bigger than that of the Brij 97-stabilized system because of the relatively less dense interfacial packing of the cationic surfactant. CTAB forms a complex with the model drugs because of ionic interaction between CTAB and the aromatic and azo groups of the model drugs. This complexation is expected to increase emulsion stability and affect model drug transport kinetics. The transport rates of model drugs in emulsions increased with increases in CTAB micellar concentrations up to 0.5% w/v and then decreased at higher surfactant concentrations. Total transport rates of phenobarbital and barbital were faster than those of phenylazoaniline and benzocaine. Excess surfactant affected the transport rates of the model drugs in the emulsions depending on drug surface activity and lipophilicity. The transport profiles of the model drugs appeared to be governed by model drug oil/water partition coefficient values and by micellar shape changes at higher surfactant concentrations.

摘要

开展了一项研究,以确定过量表面活性剂对乳液中转运动力学的影响,使用表面活性(苯巴比妥、巴比妥)和非表面活性(苯基偶氮苯胺、苯佐卡因)模型药物(pH 7.0)。选择矿物油作为油相,选择离子型表面活性剂十六烷基三甲基溴化铵(CTAB)作为乳化剂。非离子表面活性剂Brij 97对这些模型药物转运动力学的影响已由其他作者确定。使用安装有亲水性透析膜(截留分子量为1 kD和50 kD)的并排扩散池和一种新型的本体平衡反向透析袋技术,研究了模型药物在三相系统中的转运。通过使用光子相关光谱法,根据时间、温度和模型药物的存在情况对液滴大小进行分析,来确定乳液稳定性。在表面活性剂存在的情况下测定矿物油/水分配系数和水溶性。由于阳离子表面活性剂的界面堆积相对较疏松,CTAB稳定的乳液体系的液滴尺寸比Brij 97稳定的体系大。由于CTAB与模型药物的芳香族和偶氮基团之间存在离子相互作用,CTAB与模型药物形成复合物。预计这种络合作用会提高乳液稳定性并影响模型药物的转运动力学。模型药物在乳液中的转运速率随着CTAB胶束浓度增加至0.5% w/v而增加,然后在更高的表面活性剂浓度下降低。苯巴比妥和巴比妥总的转运速率比苯基偶氮苯胺和苯佐卡因快。过量表面活性剂根据药物的表面活性和亲脂性影响模型药物在乳液中的转运速率。模型药物的转运曲线似乎受模型药物油/水分配系数值以及较高表面活性剂浓度下胶束形状变化的控制。

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