DNP-enhanced Solid-state NMR Studies of Pharmaceuticals

DNP 增强的药物固态核磁共振研究

• 批准号: 2273989
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2273989
• 关键词: DNP; enhanced; Solid; state; NMR

Solid-state nuclear magnetic resonance (NMR) is a powerful method for studying the molecular structure and dynamics of a broad range of systems from heterogeneous materials to biological molecules. In some situations solid-state NMR can suffer from low sensitivity, because of the small nuclear spin polarizations involved, so that long acquisition times or large sample volumes are required. However, weak NMR signals can be dramatically enhanced by dynamic nuclear polarization (DNP), which involves transfer of electron spin polarization from radicals implanted in the sample to nearby nuclei. The substantial enhancements (up to 300-fold) obtained with DNP make NMR studies of dilute species feasible for the first time and have already prompted exciting new NMR applications to interfaces, porous materials and microcrystalline substances.The University of Nottingham has recently established a DNP-enhanced solid-state NMR Facility funded by a grant of £2.5 M from EPSRC. In this collaboration with GSK DNP-enhanced solid-state NMR will be used to study pharmaceutical formulations and drug delivery systems. These are challenging systems to study by solid-state NMR because of the often low concentration of the active pharmaceutical ingredient (API). However, the substantial signal enhancements obtained with DNP will allow natural abundance investigations of changes to polymorphs or hydration states of APIs which occur on formulation and the interactions at the interfaces between APIs and excipients which include fillers, binders, lubricants and preservatives, as well as drug delivery vehicles.

固态核磁共振 (NMR) 是研究从异质材料到生物分子等多种系统的分子结构和动力学的强大方法。在某些情况下，固态 NMR 由于尺寸较小，可能会出现灵敏度较低的问题。然而，动态核极化 (DNP) 可以显着增强微弱的 NMR 信号，动态核极化涉及电子自旋极化从注入样品中的自由基转移到附近的原子核。 .实质性的增强（高达 300 倍）DNP 的推动使得稀物质的 NMR 研究首次变得可行，并且已经在界面、多孔材料和微晶物质方面带来了令人兴奋的新 NMR 应用。诺丁汉大学最近建立了一种 DNP 增强固体获得-state NMR 设施由 EPSRC 拨款 250 万英镑资助，在与 GSK 的合作中，DNP 增强型固态 NMR 将用于研究药物配方和药物。由于活性药物成分 (API) 的浓度通常较低，因此这些系统对于通过固态 NMR 进行研究具有挑战性。然而，使用 DNP 获得的显着信号增强将允许对多晶型物或水合状态的变化进行自然丰度研究。配方中发生的 API 以及 API 和赋形剂（包括填充剂、粘合剂、润滑剂和防腐剂以及药物输送载体）之间界面的相互作用。