Nutraceuticals in Bulk and Dosage Forms: Analysis by 35Cl and 14N Solid-State NMR and DFT Calculations.

Abstract

This study uses 35Cl and 14N solid-state NMR (SSNMR) spectroscopy and dispersion-corrected plane-wave density functional theory (DFT) calculations for the structural characterization of chloride salts of nutraceuticals in their bulk and dosage forms. For eight nutraceuticals, we measure the 35Cl EFG tensor parameters of the chloride ions and use plane-wave DFT calculations to elucidate relationships between NMR parameters and molecular-level structure, which provide rapid NMR crystallographic assessments of structural features. We employ both 35Cl direct excitation and 1H→35Cl cross-polarization methods to characterize a dosage form containing α-d-glucosamine HCl, observe possible impurity and/or adulterant phases, and quantify the weight percent of the active ingredient. To complement this, we also investigate 14N SSNMR spectroscopy and DFT calculations to characterize nitrogen atoms in the nutraceuticals. This includes a discussion of targeted acquisition experimental protocols (i.e., acquiring a select region of the overall pattern that features key discontinuities) that allow ultrawideline spectra to be acquired rapidly, even for unreceptive samples (i.e., those with long values of T1(14N), short values of T2eff(14N), or very broad patterns). It is hoped that these experimental and computational protocols will be useful for the characterization of various solid forms of nutraceuticals (i.e., salts, polymorphs, hydrates, solvates, cocrystals, amorphous solid dispersions, etc.), help detect impurity and counterfeit solid phases in dosage forms, and serve as a foundation for future NMR crystallographic studies of nutraceutical solid forms, including studies using ab initio crystal structure prediction algorithms.