High resolution solid-state NMR spectroscopy offers several ways to analyze the crystal structure of drug polymorphs. Microcrystalline structures are appropriate for SS-NMR, and the method is complementary to diffraction techniques, especially when growing large single-crystals is difficult. Therefore, NMR crystallography has proved to be a powerful tool in elucidating the crystal structure of pharmaceutical drugs. It is especially beneficial when analyzing polymorphs of drugs that differ in their physiochemical properties, such as solubility, stability, and drug efficacy. Knowing the different forms of a drug is useful and necessary for pharmaceutical companies, as the FDA requires them to characterize, analyze, and identify all forms a drug can exhibit, including the most stable form. Spin-lattice relaxation is a phenomenon seen in NMR spectroscopy, and it is polymorph dependent. Spin-lattice relaxation can connect the crystal structure of a drug to its properties. We will report the results of 1H spin-lattice relaxation measurements (T1) of polymorphic forms from cimetidine, carbamazepine, erlotinib, acetaminophen, and other drugs. While SS-NMR is very effective in identifying the crystal structure of polymorphic drugs, the technique involves long data collection times, which is limiting when a high sample output is needed. Therefore, the focus of this study is to grow drug polymorphs with paramagnetic impurities, such as chromium or nickel acetylacetonate. The paramagnetic complexes serve as the relaxation centers, but do not alter the crystal structure of the polymorphic drug. The doped drug samples have decreased 1H T1 relaxation times, and, therefore, decreased data collection times. The reduced 1H T1 values also lead to spectra with enhanced signal-to-noise.

Proton spin-lattice relaxation of pharmaceutical polymorphs by high resolution solid-state NMR

255th National Meeting (2018)

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