Solid-state nuclear magnetic resonance (SS-NMR) spectroscopy was utilized in conjunction with inductively coupled plasma optical emission spectroscopy (ICP-OES) and powder X-ray diffraction (PXRD) to show that the addition of paramagnetic transition metals to polymorphs of different pharmaceutical compounds resulted in the lowering of the 1H spin-lattice relaxation time (T1). High resolution 13C cross-polarization and magic-angle-spinning using the inversion recovery sequence were used to measure T1 values for each polymorph. SS-NMR has become a common technique to study polymorphism in pharmaceutical solids, but it is hindered by its long collection time due to T1 values. ICP-OES was used to quantify the number of paramagnetic ions that were added to the polymorphs of different pharmaceutical compounds in order to discern an inverse trend in which the increase in weight fraction of paramagnetic ions resulted in a decrease in the T1 values. The degree to which both of the metal acetylacetonate complexes were incorporated into the microcrystal and their homogeneity were also investigated using ICP-OES. The addition of paramagnetic compounds does not affect polymorphic crystallinity, as shown using PXRD, or the quality of NMR spectra. Chromium (III) acetylacetonate and nickel (II) acetylacetonate were used to significantly decrease the T1 values for carbamazepine Forms I, II, III, and dihydrate, cimetidine Forms A and B, nabumetone Form I, and acetaminophen Form I polymorphs. This project has been shown to demonstrate a fast data collection that will enable high-throughput utilization of SS-NMR techniques to study polymorphic solids and therefore, could set the groundwork for NMR crystallography studies. Additionally, this approach appears to be viable for a wide range of drugs, specifically those with polymorphs with more problematic spin-lattice relaxation issues.

Using inductively coupled plasma atomic spectroscopy and solid-state NMR spectroscopy to increase characterization speed of polymorphic drugs

255th National Meeting (2018)

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