共晶
分子间力
拉曼光谱
化学
结晶学
化学物理
氢键
霉酚酸
晶体结构
溶解度
计算化学
物理化学
分子
有机化学
移植
外科
物理
光学
医学
作者
C. Wallace,Margaret P. Davis,Timothy M. Korter
出处
期刊:Pharmaceutics
[MDPI AG]
日期:2023-07-11
卷期号:15 (7): 1924-1924
被引量:2
标识
DOI:10.3390/pharmaceutics15071924
摘要
The aqueous solubility of solid-state pharmaceuticals can often be enhanced by cocrystallization with a coformer to create a binary cocrystal with preferred physical properties. Greater understanding of the internal and external forces that dictate molecular structure and intermolecular packing arrangements enables more efficient design of new cocrystals. Low-frequency (sub-200 cm−1) Raman spectroscopy experiments and solid-state density functional theory simulations have been utilized together to investigate the crystal lattice vibrations of mycophenolic acid, an immunosuppressive drug, in its pure form and as a cocrystal with 2,2′-dipyridylamine. The lattice vibrations primarily consist of large-amplitude translations and rotations of the crystal components, thereby providing insights into the critical intermolecular forces governing cohesion of the molecular solids. The simulations reveal that despite mycophenolic acid having a significantly unfavorable conformation in the cocrystal as compared to the pure solid, the cocrystal exhibits greater thermodynamic stability over a wide temperature range. The energetic penalty due to the conformational strain is more than compensated for by the strong intermolecular forces between the drug and 2,2′-dipyridylamine. Quantifying the balance of internal and external energy factors in cocrystal formation indicates a path forward in the development of future mycophenolic acid cocrystals.
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