Bebiano Suse S, Ter Horst Joop H, Oswald Iain D H
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, U.K.
EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation, Technology Innovation Centre, University of Strathclyde, 99 George Street, Glasgow G1 1RD, U.K.
Cryst Growth Des. 2020 Oct 7;20(10):6731-6744. doi: 10.1021/acs.cgd.0c00871. Epub 2020 Aug 25.
Understanding polymorphism in chiral systems for drug manufacturing is essential to avoid undesired therapeutic effects. Generally, polymorphism is studied through changes in temperature and solution concentration. A less common approach is the application of pressure. The goal of this work is to investigate the effect of pressure on levetiracetam (pure enantiomer) and etiracetam (racemic compound). Anisotropic compressions of levetiracetam and etiracetam are observed to 5.26 and 6.29 GPa, respectively. The most compressible direction for both was identified to be perpendicular to the layers of the structure. Raman spectroscopy and an analysis of intermolecular interactions suggest subtle phase transitions in levetiracetam (∼2 GPa) and etiracetam (∼1.5 GPa). The stability of etiracetam increases with respect to levetiracetam on compression; hence, the chiral resolution of this system is unfavorable using pressure. This work contributes to the ongoing efforts in understanding the stability of chiral systems.
了解药物制造中手性体系的多晶型对于避免不良治疗效果至关重要。一般来说，多晶型是通过温度和溶液浓度的变化来研究的。一种不太常见的方法是施加压力。这项工作的目的是研究压力对左乙拉西坦（纯对映体）和乙拉西坦（外消旋化合物）的影响。观察到左乙拉西坦和乙拉西坦的各向异性压缩分别达到5.26 GPa和6.29 GPa。两者最易压缩的方向被确定为垂直于结构层。拉曼光谱和分子间相互作用分析表明，左乙拉西坦（约2 GPa）和乙拉西坦（约1.5 GPa）存在细微的相变。压缩时，乙拉西坦相对于左乙拉西坦的稳定性增加；因此，利用压力对该体系进行手性拆分是不利的。这项工作有助于持续努力了解手性体系的稳定性。
