Sheth Agam R, Lubach Joseph W, Munson Eric J, Muller Francis X, Grant David J W
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455-0343, USA.
J Am Chem Soc. 2005 May 11;127(18):6641-51. doi: 10.1021/ja045823t.
Structural and solid-state changes of piroxicam in its crystalline form under mechanical stress were investigated using cryogenic grinding, powder X-ray diffractometry, diffuse-reflectance solid-state ultraviolet-visible spectroscopy, variable-temperature solid-state (13)C nuclear magnetic resonance spectroscopy, and solid-state diffuse-reflectance infrared Fourier transform spectroscopy. Crystalline piroxicam anhydrate exists as colorless single crystals irrespective of the polymorphic form and contains neutral piroxicam molecules. Under mechanical stress, these crystals become yellow amorphous piroxicam, which has a strong propensity to recrystallize to a colorless crystalline phase. The yellow color of amorphous piroxicam is attributed to charged piroxicam molecules. Variable-temperature solid-state (13)C NMR spectroscopy indicates that most of the amorphous piroxicam consists of neutral piroxicam molecules; the charged species comprise only about 8% of the amorphous phase. This ability to quantify the fractions of charged and neutral molecules of piroxicam in the amorphous phase highlights the unique capability of solid-state NMR to quantify mixtures in the absence of standards. Other compounds of piroxicam, which are yellow, are known to contain zwitterionic piroxicam molecules. The present work describes a system in which proton transfer accompanies both solid-state disorder and a change in color induced by mechanical stress, a phenomenon which may be termed mechanochromism of piroxicam.
采用低温研磨、粉末X射线衍射、漫反射固态紫外-可见光谱、变温固态（13）C核磁共振光谱以及固态漫反射红外傅里叶变换光谱等方法，研究了吡罗昔康晶体形式在机械应力作用下的结构和固态变化。无论多晶型如何，无水吡罗昔康晶体均以无色单晶形式存在，且含有中性吡罗昔康分子。在机械应力作用下，这些晶体变成黄色无定形吡罗昔康，其具有强烈的重结晶为无色晶相的倾向。无定形吡罗昔康的黄色归因于带电的吡罗昔康分子。变温固态（13）C核磁共振光谱表明，大多数无定形吡罗昔康由中性吡罗昔康分子组成；带电物种仅占无定形相的约8%。这种量化无定形相中吡罗昔康带电和中性分子分数的能力突出了固态核磁共振在无标准物情况下量化混合物的独特能力。已知吡罗昔康的其他黄色化合物含有两性离子吡罗昔康分子。本研究描述了一个质子转移伴随着固态无序和机械应力引起的颜色变化的系统，这种现象可称为吡罗昔康的机械变色。
