Programa de Pós-Graduação em Química, Universidade Federal Fluminense, Outeiro São João Batista, s/n°, 24210-130 Niterói, Brazil; Laboratório de Micro e Nanotecnologia, Farmanguinhos/Fiocruz, Av. Brasil, 4036, 21040-361 Rio de Janeiro, Brazil.
Laboratório de Micro e Nanotecnologia, Farmanguinhos/Fiocruz, Av. Brasil, 4036, 21040-361 Rio de Janeiro, Brazil.
Int J Pharm. 2018 Dec 20;553(1-2):261-271. doi: 10.1016/j.ijpharm.2018.10.051. Epub 2018 Oct 23.
The drug carvedilol, used to treat cardiovascular conditions, is known to exist in distinct crystalline forms. Polymorphs II and III and the hydrate are characterized by variations in their molecular packing and conformation. This study deals with the spectroscopic (supported by quantum chemistry calculations) characterization of carvedilol structures. Band assignments were performed considering the isolated molecules and periodic calculations. We discuss the correlation between the vibrational modes and the intermolecular forces in the crystalline structures. Towards a better understanding of the intermolecular interactions, Hirshfeld surface was used. Besides band shifts related to stretching vibrations of N-H and O-H groups, differences between other modes have shown the possibility of using infrared spectroscopy to distinguish the crystal forms; technique routinely used in quality control of pharmaceutics. According to the spectroscopic analysis, the N-H groups participate in stronger bonds in the polymorph III, which contributes to its greater stability. With Hirshfeld surface we concluded that the bond with the nitrogen of the aliphatic chain participating as hydrogen acceptor in polymorph II is responsible for the pointy peaks in the fingerprint plot. This can explain why polymorph II shows lower dissolution in acid medium, as described in a previous work of our group.
用于治疗心血管疾病的药物卡维地洛已知存在不同的晶型。晶型 II 和 III 以及水合物的特征在于其分子堆积和构象的变化。本研究涉及对卡维地洛结构的光谱（由量子化学计算支持）表征。在考虑孤立分子和周期性计算的情况下进行了带分配。我们讨论了晶状结构中振动模式与分子间力之间的相关性。为了更好地理解分子间相互作用，使用了 Hirshfeld 表面。除了与 N-H 和 O-H 基团伸缩振动相关的频带位移外，其他模式的差异表明了使用红外光谱来区分晶体形态的可能性；这是制药质量控制中常用的技术。根据光谱分析，N-H 基团在晶型 III 中参与更强的键，这有助于其更稳定。通过 Hirshfeld 表面，我们得出结论，在晶型 II 中，与脂肪链的氮原子作为氢键受体结合的键负责在指纹图谱中出现尖峰。这可以解释为什么我们之前的研究小组描述的晶型 II 在酸性介质中的溶解率较低。
