Neugebauer Peter, Cardona Javier, Besenhard Maximilian O, Peter Anna, Gruber-Woelfler Heidrun, Tachtatzis Christos, Cleary Alison, Andonovic Ivan, Sefcik Jan, Khinast Johannes G
Graz University of Technology, Institute of Process and Particle Engineering, Inffeldgasse 13, 8010 Graz, Austria.
Centre for Intelligent Dynamic Communications, Department of Electronic and Electrical Engineering, University of Strathclyde, Royal College Building, 204 George Street, Glasgow, G1 1XW, U.K.
Cryst Growth Des. 2018 Aug 1;18(8):4403-4415. doi: 10.1021/acs.cgd.8b00371. Epub 2018 Jun 15.
Besides size and polymorphic form, crystal shape takes a central role in engineering advanced solid materials for the pharmaceutical and chemical industries. This work demonstrates how multiple cycles of growth and dissolution can manipulate the habit of an acetylsalicylic acid crystal population. Considerable changes of the crystal habit could be achieved within minutes due to rapid cycling, i.e., up to 25 cycles within <10 min. The required fast heating and cooling rates were facilitated using a tubular reactor design allowing for superior temperature control. The face-specific interactions between solvent and the crystals' surface result in face-specific growth and dissolution rates and hence alterations of the final shape of the crystals in solution. Accurate quantification of the crystal shapes was essential for this work, but is everything except simple. A commercial size and shape analyzer had to be adapted to achieve the required accuracy. Online size, and most important shape, analysis was achieved using an automated microscope equipped with a flow-through cell, in combination with a dedicated image analysis routine for particle tracking and shape analysis. Due to the implementation of this analyzer, capable of obtaining statistics on the crystals' shape while still in solution (no sampling and manipulation required), the dynamic behavior of the size shape distribution could be studied. This enabled a detailed analysis of the solvent's effect on the change in crystal habit.
除了尺寸和多晶型形式外，晶体形状在制药和化工行业先进固体材料的工程设计中起着核心作用。这项工作展示了多个生长和溶解循环如何控制乙酰水杨酸晶体群体的习性。由于快速循环，即在不到10分钟内进行多达25个循环，晶体习性在几分钟内就可以发生显著变化。使用允许卓越温度控制的管式反应器设计实现了所需的快速加热和冷却速率。溶剂与晶体表面之间的面特异性相互作用导致面特异性生长和溶解速率，从而改变溶液中晶体的最终形状。准确量化晶体形状对这项工作至关重要，但绝非易事。必须对商用尺寸和形状分析仪进行改装以达到所需的精度。使用配备流通池的自动显微镜结合用于颗粒跟踪和形状分析的专用图像分析程序，实现了在线尺寸以及最重要的形状分析。由于该分析仪的实施，能够在晶体仍处于溶液状态时（无需采样和操作）获取有关晶体形状的统计数据，因此可以研究尺寸形状分布的动态行为。这使得能够详细分析溶剂对晶体习性变化的影响。
