DNP-enhanced Solid-state NMR Studies of Pharmaceuticals

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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.