Tetramethylpyrazine Cocrystals with Cinnamic Acid and Its Derivatives: Crystal Structures, Theoretical Computations, and Sublimation Behavior Studies

• DOI: 10.1021/acs.cgd.4c00227
• Publication Date: 2024-08-16T06:42:40Z
• Authors: Fei Wang; Jianhong Liu; Yuxin Xie; Xiaohua Chen; Lianchao Liu; Xin He; Xinghua Zhao
• Keywords: Cocrystal; Sublimation; Rational design; Tetramethylpyrazine; Cinnamic acid

Tetramethylpyrazine (TMP) is used clinically to treat cardiovascular disease and ischemic cerebrocardial vascular disease. However, the high sublimation tendency of TMP leads its physical instability. In this study, we successfully synthesized comprehensively characterized four cocrystals formed by with cinnamic acid derivatives. These effectively mitigated TMP, demonstrating their potential for stabilizing active pharmaceutical ingredient. Through detailed density functional theory calculations, systematically investigated stability mechanisms these cocrystals, revealing that both number distribution polar groups, governing formation strong hydrogen bonds, presence weak bonds jointly contribute stability. Furthermore, explored intricate relationships among cocrystal stability, bonding patterns, crystal growth mechanisms, offering novel avenues rational design optimization in drug development. This study not only enhances our understanding but also provides valuable insights innovation, paving way future theoretical guidance practical references optimization.