DNP-enhanced Solid-state NMR Studies of Pharmaceuticals

固体核磁共振是研究从非均相材料到生物分子等多种体系的分子结构和动力学的有力手段。在某些情况下，固态核磁共振可能会受到低灵敏度的影响，因为涉及到小的核自旋极化，因此需要长时间的采集时间或大的样本量。然而，动态核极化(DNP)可以显著增强微弱的核磁共振信号，动态核极化涉及电子自旋极化从注入到样品中的自由基转移到附近的原子核。DNP获得的实质性增强(高达300倍)使稀物种的核磁共振研究首次成为可能，并已促进了令人兴奋的新的核磁共振在界面、多孔材料和微晶材料中的应用。诺丁汉大学最近建立了一个DNP增强的固态核磁共振设施，资金来自EPSRC的GB 2.5M。在与葛兰素史克的合作中，DNP增强的固态核磁共振将用于研究药物配方和药物输送系统。由于活性药物成分(API)的浓度往往很低，这些都是通过固态核磁共振进行研究的具有挑战性的系统。然而，DNP获得的实质性信号增强将使人们能够自然地研究原料药在配方上发生的多晶型或水合状态的变化，以及原料药与辅料(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的界面相互作用。

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.