DNP-enhanced Solid-state NMR Studies of Pharmaceuticals

固态核磁共振（NMR）是研究从非均质材料到生物分子的广泛系统的分子结构和动力学的有力方法。在某些情况下，固态NMR可能会受到低灵敏度的影响，因为所涉及的核自旋极化很小，因此需要长的采集时间或大的样品体积。然而，弱NMR信号可以通过动态核极化（DNP）显著增强，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核。与DNP获得的实质性增强（高达300倍），使NMR研究的稀释物种可行的第一次，并已促使令人兴奋的新的NMR应用接口，多孔材料和微晶substances.The诺丁汉大学最近建立了一个DNP增强固态NMR Facility资助的£2.5 M从EPSRC的赠款。在与GSK的合作中，DNP增强的固态NMR将用于研究药物制剂和药物递送系统。由于活性药物成分（API）的浓度通常较低，因此通过固态NMR研究这些系统具有挑战性。然而，使用DNP获得的显著信号增强将允许对在制剂上发生的API的多晶型物或水合状态的变化以及API与赋形剂（包括填充剂、粘合剂、润滑剂和防腐剂以及药物递送载体）之间的界面处的相互作用进行自然丰度研究。

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.