Natural abundance ¹⁴N and ¹⁵N solid-state NMR of pharmaceuticals and their polymorphs

Abstract

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14N Solid‐State NMR Spectroscopy of Amino Acids

“…Upon extractingt he 14 Nq uadrupolarp arameters from the powder patterns, only the magnitude of C Q ,b ut not its sign, can be determined. We refer the reader to our recent publication for furtherd iscussion [52] 7. 14 NSSNMR spectra of amino acids having low or intermediate h Q values may displayl ower signal intensity near the Larmorf requency (i.e.,t he center of the Pake-like pattern).…”

“…Several cases of polymorph differentiation by using 14 NN QR have been reported, [70][71][72][73][74][75][76] and we previouslyd emonstrated the use of UW 14 NSSNMR to differentiate polymorphs of glycine andv arious active pharmaceutical ingredients based on unique sets of quadrupolarp arameters and variation in T 2 eff ( 14 N) relaxation constants. [8,52] l-Histidine has two polymorphic forms at room temperature; A-histidine (A-his) has an orthorhombic unit cell with P2 1 2 1 (Table S1). However,t he polymorphs can also be distinguished by ad ifference in the T 2 eff ( 14 N) relaxationb ehavior, which results in different S/ Nr atios for their respective spectra( the ratio of S/N values in the spectra of A-his to B-his is % 0.6).…”

DNP‐enhanced solid‐state NMR spectroscopy of active pharmaceutical ingredients

“…The availability of high‐field NMR systems and specialized pulse sequences has enabled solid‐state NMR experiments on APIs with quadrupolar nuclei such as 7 Li, 14 N, 17 O, 23 Na, and 35 Cl . For example, Schurko and coworkers have demonstrated that 35 Cl solid‐state NMR spectroscopy can be applied to hydrochloride salts of APIs to differentiate polymorphs and detect APIs within dosage forms .…”

Deracemization in a Complex Quaternary System with a Second‐Order Asymmetric Transformation by Using Phase Diagram Studies

“…Access to the desired polymorph and enantiomer of a particular compound is a critical issue in the field of pharmaceutical chemistry owing to the differences in bioavailability and bioactivity of polymorphs and enantiomers. Among the 42 drugs with chemical entities approved by the Food and Drug Administration (FDA) in 2018, 25 molecules contain a chiral center, and over 80 % of the active pharmaceutical ingredients (APIs) exhibit polymorphism or solvate formation and may show differences in physical properties, which makes chiral separation and polymorph control vital aspects of drug development. Classical chiral resolution techniques such as diastereomeric resolutions mediated by chemical transformation are robust and reliable approaches to the preparation of enantiomerically pure materials and are preferentially used in industrial chemistry.…”