von Corswant C, Thorén P, Engström S
Astra Hässle AB, Mölndal, Sweden.
J Pharm Sci. 1998 Feb;87(2):200-8. doi: 10.1021/js970258w.
A pharmaceutically acceptable microemulsion system composed of a medium-chain triglyceride (MCT), soybean phosphatidylcholine and poly(ethylene glycol)(660)-12-hydroxystearate (12-HSA-EO15) as amphiphiles, and poly(ethylene glycol) 400 (PEG 400) and ethanol as cosolvents is presented and characterized in terms of phase behavior, microstructure, solubilization capacity and in vivo effects after intravenous administration to conscious rats. At a total concentration of 11.9 wt % of soybean phosphatidylcholine and 12-HSA-EO15, a microemulsion region was formed over a wide range of alpha, where alpha is the weight fraction of MCT/(MCT + water + PEG 400 + ethanol). The microstructure of the microemulsion was of a bicontinuous nature even at high oil concentrations. The mean droplet diameter of the oil-in-water emulsion formed after dilution of microemulsions prepared at different alpha within the one-phase region was between 60 and 200 nm. It was concluded that it is possible to administer up to 0.5 mL/kg of the microemulsion (alpha = 0.5) without producing any significant effect on acid-base balance, blood gases, plasma electrolytes, mean arterial blood pressure (MAP), heart rate (HR), and PQ time (the time between depolarization of atrium and chamber). At a dose of 1.5 mL/kg, a temporary increase in MAP, a decrease in HR, and a prolongation of the PQ time were observed.
提出了一种由中链甘油三酯（MCT）、大豆磷脂酰胆碱和聚（乙二醇）（660）-12-羟基硬脂酸酯（12-HSA-EO15）作为两亲物，以及聚（乙二醇）400（PEG 400）和乙醇作为助溶剂组成的药学上可接受的微乳液系统，并对其相行为、微观结构、增溶能力以及静脉注射给清醒大鼠后的体内效应进行了表征。在大豆磷脂酰胆碱和12-HSA-EO15的总浓度为11.9 wt%时，在较宽的α范围内形成了微乳液区域，其中α是MCT/（MCT+水+PEG 400+乙醇）的重量分数。即使在高油浓度下，微乳液的微观结构也是双连续性质的。在单相区域内不同α值下制备的微乳液稀释后形成的水包油乳液的平均液滴直径在60至200 nm之间。得出的结论是，静脉注射高达0.5 mL/kg的微乳液（α=0.5）对酸碱平衡、血气、血浆电解质、平均动脉血压（MAP）、心率（HR）和PQ时间（心房和心室去极化之间的时间）不会产生任何显著影响。在剂量为1.5 mL/kg时，观察到MAP暂时升高、HR降低以及PQ时间延长。
