Solid-state nuclear magnetic resonance pharmaceutical formulations

Solid-state nuclear magnetic resonance (SSNMR) spectroscopy is a powerful technique used in the analysis of solids, and is currently finding more and more applications, particularly in the analysis of pharmaceutical formulations. It is a non-destructive, non-invasive technique that can be employed to simultaneously examine the physical and chemical states of both the active pharmaceutical ingredient (API) and the excipients present as they exist within the formulation. It is also highly selective, as nuclei of the API often have different chemical shifts than do common excipients. 

Solid-state nuclear magnetic resonance (NMR) is nowadays an established technique in the pharmaceutical industry, used mainly as a tool to distinguish different polymorphs. Its advantages are high versatility and resolution, which allow for studies of aU the materials in a formulation. Compared to, for example, powder XRPD and Raman scattering, spectral overlap is most often much less of a problem in NMR. Also, the primary parameter, the resonance frequency or the chemical shift, is very sensitive not only to the intramolecular structure but also to intermolecular interactions and spatial arrangement, which is the basis for polymorph selectivity. A range of nuclei can be studied for complementary information, for example, H, N, and T. 

Nuclear magnetic resonance (NMR) spectroscopy has become a fundamental technique for pharmaceutical analysis (1-8). Typically, when one thinks of NMR spectroscopy, solution-phase studies, such as structure elucidation, immediately come to mind (1). Within a drug discovery setting, structure elucidation is the one of the primary uses of NMR. It is ironic to think that although approximately 80% of all pharmaceutical products are solid-state formulations, solid-state NMR is relatively new to pharmaceutical analysis. Based on the myriad of uses of NMR spectroscopy as applied to pharmaceutical analysis, this chapter focuses on the use of solid-state NMR for the analysis of pharmaceuticals. 

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