Use of Dynamic Nuclear Polarisation Nuclear Magnetic Resonance (DNP NMR) for Advanced Solid-State Structural Characterisation of Active Pharmaceutical

从异质材料到生物材料的广泛系统的分子结构和动力学。在某些情况下，固态核磁共振可能会受到低灵敏度的影响，因为涉及到较小的核自旋极化，因此需要较长的采集时间或较大的样本量。然而，动态核极化（DNP）可以显著增强弱核磁共振信号，这涉及到从注入样品的自由基到附近原子核的电子自旋极化转移。DNP获得的实质性增强（高达300倍）使稀释物质的核磁共振研究首次成为可能，并已促使令人兴奋的新核磁共振应用于界面，多孔材料和微晶物质。诺丁汉大学最近建立了一个dnp增强的固态核磁共振设备，由EPSRC拨款250万英镑资助。在与GSK的合作中，dnp增强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）的浓度较低，因此固态核磁共振对这些体系的研究具有挑战性。然而，DNP获得的大量信号增强将允许对原料药和赋形剂（包括填料、粘合剂、润滑剂和防腐剂以及药物递送载体）的多态或水合状态变化进行自然丰度调查。

molecular structure and dynamics of a broad range of systems from heterogeneous materials to biological materials. In some situations the solid-state NMR can suffer from low sensitivity, because of the small nuclear spin polarizations involved, so that long acquisition times or large samples 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 £2.5m 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 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 and excipients which include fillers, binders, lubricants and preservatives, as well as drug delivery vehicles.