Campus Units

Chemistry

Document Type

Article

Publication Version

Accepted Manuscript

Publication Date

2016

Journal or Book Title

Physical Chemistry Chemical Physics

Volume

18

First Page

25893

Last Page

25904

DOI

10.1039/c6cp04353d

Abstract

In this work, we show how to obtain efficient dynamic nuclear polarization (DNP) enhanced 35Cl solid-state NMR (SSNMR) spectra at 9.4 T and demonstrate how they can be used to characterize the molecular-level structure of hydrochloride salts of active pharmaceutical ingredients (APIs) in both bulk and low wt% API dosage forms. 35Cl SSNMR central-transition powder patterns of chloride ions are typically tens to hundreds of kHz in breadth, and most cannot be excited uniformly with high-power rectangular pulses or acquired under conditions of magic-angle spinning (MAS). Herein, we demonstrate the combination of DNP and 1H–35Cl broadband adiabatic inversion cross polarization (BRAIN-CP) experiments for the acquisition of high quality wideline spectra of APIs under static sample conditions, and obtain signals up to 50 times greater than in spectra acquired without the use of DNP at 100 K. We report a new protocol, called spinning-on spinning-off (SOSO) acquisition, where MAS is applied during part of the polarization delay to increase the DNP enhancements and then the MAS rotation is stopped so that a wideline 35Cl NMR powder pattern free from the effects of spinning sidebands can be acquired under static conditions. This method provides an additional two-fold signal enhancement compared to DNP-enhanced SSNMR spectra acquired under purely static conditions. DNP-enhanced 35Cl experiments are used to characterize APIs in bulk and dosage forms with Cl contents as low as 0.45 wt%. These results are compared to DNP-enhanced 1H–13C CP/MAS spectra of APIs in dosage forms, which are often hindered by interfering signals arising from the binders, fillers and other excipient materials

Comments

This is an article from Hirsh, David A., Aaron J. Rossini, Lyndon Emsley, and Robert W. Schurko. "35 Cl dynamic nuclear polarization solid-state NMR of active pharmaceutical ingredients." Physical Chemistry Chemical Physics 18, no. 37 (2016): 25893-25904. doi: 10.1039/c6cp04353d. Posted with permission.

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Copyright Owner

Royal Society of Chemistry

Language

en

File Format

application/pdf

Included in

Chemistry Commons

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