On the one hand, we use small molecule samples in the solid state to test the feasability and limits of specific NMR experiments for the subsequent investigation of drug-polymer formulations. On the other hand, we study the drug molecules separately using NMR Crystallography to gain insights into preferred interaction partners and the influence of different molecular arragements on NMR parameters. For that purpose, we also take a look at polymorphs, solvates and co-crystalline forms of the drug molecules thus complementing our understanding of the investigated compounds.
A structural model (often based on XRD data) is first geometry optimized before GIPAW (CASTEP) calculations yield a range of NMR parameters, which can be subsequently compared to experimental solid-state NMR data. This combination of experimental and calculated data helps us to detect polymorphic transformations and assign crowded spectra, in particular, for compounds with more than one molecule in the asymmetric crystallographic unit (Z' > 1). Furthermore, comparison between calculated NMR parameters for full crystal structures and separated individual molecules helps to predict changes in the experimental data to be expected upon variation of the coordination environment.
A throrough understanding of the individual drugs is a prerequisite for the more complex analysis of the formulations.