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research article

Cl-35 dynamic nuclear polarization solid-state NMR of active pharmaceutical ingredients

Hirsh, David A.
•
Rossini, Aaron J.  
•
Emsley, Lyndon  
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2016
Physical Chemistry Chemical Physics

In this work, we show how to obtain efficient dynamic nuclear polarization (DNP) enhanced Cl-35 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. Cl-35 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 H-1-Cl-35 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 Cl-35 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 Cl-35 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 H-1-C-13 CP/MAS spectra of APIs in dosage forms, which are often hindered by interfering signals arising from the binders, fillers and other excipient materials.

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Type
research article
DOI
10.1039/c6cp04353d
Web of Science ID

WOS:000385172600015

Author(s)
Hirsh, David A.
•
Rossini, Aaron J.  
•
Emsley, Lyndon  
•
Schurko, Robert W.
Date Issued

2016

Publisher

Royal Society of Chemistry

Published in
Physical Chemistry Chemical Physics
Volume

18

Issue

37

Start page

25893

End page

25904

Peer reviewed

REVIEWED

Written at

OTHER

EPFL units
LRM  
Available on Infoscience
November 21, 2016
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/131402
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