Solid-state NMR spectroscopy has become a valuable tool for the characterization of both pure and formulated active pharmaceutical ingredients (APIs). However, NMR generally suffers from poor sensitivity that often restricts NMR experiments to nuclei with favorable properties, concentrated samples, and acquisition of one-dimensional (1D) NMR spectra. Here, we review how dynamic nuclear polarization (DNP) can be applied to routinely enhance the sensitivity of solid-state NMR experiments by one to two orders of magnitude for both pure and formulated APIs. Sample preparation protocols for relayed DNP experiments and experiments on directly doped APIs are detailed. Numerical spin diffusion models illustrate the dependence of relayed DNP enhancements on the relaxation properties and particle size of the solids and can be used for particle size determination when the other factors are known. We then describe the advanced solid-state NMR experiments that have been enabled by DNP and how they provide unique insight into the molecular and macroscopic structure of APIs. For example, with large sensitivity gains provided by DNP, natural isotopic abundance, (13) C-(13) C double-quantum single-quantum homonuclear correlation NMR spectra of pure APIs can be routinely acquired. DNP also enables solid-state NMR experiments with unreceptive quadrupolar nuclei such as (2) H, (14) N, and (35) Cl that are commonly found in APIs. Applications of DNP-enhanced solid-state NMR spectroscopy for the molecular level characterization of low API load formulations such as commercial tablets and amorphous solid dispersions are described. Future perspectives for DNP-enhanced solid-state NMR experiments on APIs are briefly discussed.
Analysis of Molecular Orientation in Organic Semiconducting Thin Films Using Static Dynamic Nuclear Polarization Enhanced Solid-State NMR Spectroscopy #DNPNMR
From The DNP-NMR Blog:
Analysis of Molecular Orientation in Organic Semiconducting Thin Films Using Static Dynamic Nuclear Polarization Enhanced Solid-State NMR Spectroscopy #DNPNMR
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Suzuki, K., et al., Analysis of Molecular Orientation in Organic Semiconducting Thin Films Using Static Dynamic Nuclear Polarization Enhanced Solid-State NMR Spectroscopy. Angew. Chem. Int. Ed., 2017. 56(47): p. 14842-14846.
https://www.ncbi.nlm.nih.gov/pubmed/28994190
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01-11-2018 03:11 AM
In Situ Characterization of Pharmaceutical Formulations by Dynamic Nuclear Polarization Enhanced MAS NMR #DNPNMR
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In Situ Characterization of Pharmaceutical Formulations by Dynamic Nuclear Polarization Enhanced MAS NMR #DNPNMR
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Ni, Q.Z., et al., In Situ Characterization of Pharmaceutical Formulations by Dynamic Nuclear Polarization Enhanced MAS NMR. The Journal of Physical Chemistry B, 2017. 121(34): p. 8132-8141.
http://dx.doi.org/10.1021/acs.jpcb.7b07213
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12-09-2017 07:49 AM
Oxygen-17 dynamic nuclear polarisation enhanced solid-state NMR spectroscopy at 18.8 T #DNPNMR
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Oxygen-17 dynamic nuclear polarisation enhanced solid-state NMR spectroscopy at 18.8 T #DNPNMR
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Brownbill, N.J., et al., Oxygen-17 dynamic nuclear polarisation enhanced solid-state NMR spectroscopy at 18.8 T. Chem Commun (Camb), 2017. 53(17): p. 2563-2566.
https://www.ncbi.nlm.nih.gov/pubmed/28184389
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06-10-2017 05:21 PM
DNP-Enhanced Ultrawideline Solid-State NMR Spectroscopy: Studies of Platinum in Metal-Organic Frameworks #DNPNMR
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DNP-Enhanced Ultrawideline Solid-State NMR Spectroscopy: Studies of Platinum in Metal-Organic Frameworks #DNPNMR
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Kobayashi, T., et al., DNP-Enhanced Ultrawideline Solid-State NMR Spectroscopy: Studies of Platinum in Metal-Organic Frameworks. J Phys Chem Lett, 2016. 7(13): p. 2322-7.
https://www.ncbi.nlm.nih.gov/pubmed/27266444
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01-12-2017 03:48 AM
35Cl dynamic nuclear polarization solid-state NMR of active pharmaceutical ingredients #DNPNMR
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35Cl dynamic nuclear polarization solid-state NMR of active pharmaceutical ingredients #DNPNMR
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Hirsh, D.A., et al., 35Cl dynamic nuclear polarization solid-state NMR of active pharmaceutical ingredients. Phys Chem Chem Phys, 2016. 18(37): p. 25893-25904.
https://www.ncbi.nlm.nih.gov/pubmed/27711465
Static DNP-NMR Spectroscopy to Characterize Active Pharmaceutical Ingredients #DNPNMR
From The DNP-NMR Blog:
Static DNP-NMR Spectroscopy to Characterize Active Pharmaceutical Ingredients #DNPNMR
Dynamic Nuclear Polarization in general is no new method, but the focus of modern applications has initially been on bio-macromolecules under magic-angle-spinning (MAS) conditions.
One application that came out-of-the-blue was using DNP-NMR spectroscopy to study surface materials by DNP-NMR spectroscopy (for example Lafon et al., 2011) opening up a complete new research area within material science that traditionally struggled with very low signal-to-noise (S/N) ratios.
DNP-enhanced solid-state NMR spectroscopy of active pharmaceutical ingredients #DNPNMR
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