Department of Chemistry, Materials and Chemical Engineering "G. Natta", Politecnico di Milano, Piazza L. da Vinci 32, 20133 Milano, Italy.
Department of Chemistry, Materials and Chemical Engineering "G. Natta", Politecnico di Milano, Piazza L. da Vinci 32, 20133 Milano, Italy.
Int J Pharm. 2020 Oct 15;588:119775. doi: 10.1016/j.ijpharm.2020.119775. Epub 2020 Aug 15.
Amitriptyline (AMT) and cyclobenzaprine (CBZ) are tricyclic drugs used as antidepressant and muscle relaxant, respectively. They show inherently chirality, i.e. they are chiral due to the lack of any symmetry element. As they are used as racemic mixture, diastereomeric inclusion complexes are formed via encapsulation in homochiral βCD. In this work we show that a suitable combination of NMR methods easily provides details on the chiral recognition, geometry of complexation, rotational dynamics and spatial proximity of selected atom pairs. In particular, we show that C NMR can be used to unambiguously assess chiral recognition, demonstrating a higher performance over H NMR. The mole fraction of the bound drug and the association constant can be worked out through diffusion experiments, whereas the combination of non-selective, selective and bi-selective relaxation spectra gave insights into the rotational motion of the complexed drug and the spatial proximity of selected proton pairs. The toolkit here proposed provides a thorough characterization of CD/drug inclusion complexes from a physicochemical point of view. This can constructively complement the conventional pharmacological and pharmacokinetic experiments, and can shed light on the understanding of CD/drug formulations.
阿米替林（AMT）和环苯扎林（CBZ）分别是用作抗抑郁药和肌肉松弛剂的三环类药物。它们具有固有手性，即由于缺乏任何对称元素而具有手性。由于它们被用作外消旋混合物，因此通过在同种手性β-CD 中包封形成非对映体包合复合物。在这项工作中，我们表明，适当的 NMR 方法组合可以轻松提供有关手性识别、络合几何形状、旋转动力学和所选原子对空间接近度的详细信息。特别是，我们表明 C NMR 可用于明确评估手性识别，其性能优于 H NMR。可以通过扩散实验计算出结合药物的摩尔分数和缔合常数，而非选择性、选择性和双选择性弛豫谱的组合则深入了解了复合物药物的旋转运动和所选质子对的空间接近度。这里提出的工具包从物理化学角度全面表征了 CD/药物包合复合物。这可以与传统的药理学和药代动力学实验相辅相成，并有助于理解 CD/药物制剂。
