皮罗西卡姆的机色化伴随着通过光谱方法探测的分子间质子转移和固体相变化
Agam R Sheth1, Joseph W Lubach, Eric J Munson
1Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455-0343, USA.
Journal of the American Chemical Society
|May 5, 2005
概括
机械应力将晶体皮洛克萨姆转化为黄色的无形皮洛克萨姆,归因于带电分子. 这种机械色谱,通过固态NMR量化,突出显示了机械应力诱导障碍期间的质子转移.
科学领域:
- 固态化学 固态化学
- 材料科学是一种材料科学.
- 物理化学 物理化学
背景情况:
- 皮洛西卡姆是一种非类固醇抗炎药物,表现出不同的固态形式.
- 了解压力下的结构变化对于药物的稳定性和配方至关重要.
- 之前的研究指出,黄色的皮洛西卡姆形式含有zwitterionic分子.
研究的目的:
- 为了研究在机械应力下结晶型皮罗西卡姆的结构和固态变化.
- 阐明机械应力引起的颜色变化背后的机制.
- 量化存在于无形阶段的分子物种.
主要方法:
- 低温研磨以诱导机械应力.
- 粉末X射线衍光测量 (PXRD) 用于结构分析.
- 固态UV-Vis光谱检测颜色变化.
- 可变温度固态 (13)C核磁共振 (NMR) 谱学用于分子量化.
- 固态扩散反射红外里埃变换光谱 (DRIFTS) 用于功能组分析.
主要成果:
- 机械应力将无色的晶体piroxicam无水酸转化为黄色的无形piroxicam.
- 无形皮洛西卡姆的黄色颜色与充电的皮洛西卡姆分子有关.
- 可变温度固态 (13) C NMR 显示无形阶段含有约 8% 充电的皮罗西卡姆分子.
- 无色Piroxicam显示出一种倾向于重新结晶成为无色的晶体阶段.
结论:
- 机械应力诱导Piroxicam的机色,涉及质子转移和颜色从无色变为黄色.
- 固态核磁共振是一种强大的工具,用于在无标准的无形药物阶段量化中性和带电物种.
- 这项研究表明,机械应力,固态障碍,质子转移和皮罗西卡姆的颜色变化之间存在直接联系.
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