Issue 39, 2021

Taming the dynamics in a pharmaceutical by cocrystallization: investigating the impact of the coformer by solid-state NMR

Abstract

Pharmaceuticals in their crystalline state may display a range of dynamics that can affect their physicochemical properties and chemical stability. With pharmaceutical cocrystals continuing to gain attention, there is an opportunity to investigate how the dynamics are changing in these new solid forms. Here, we investigate the dynamics in efavirenz, an anti-HIV drug, and a series of its cocrystals using a combination of DFT calculations and solid-state magic-angle spinning (MAS) NMR spectroscopy. We show that the crystalline form of efavirenz has a highly dynamic cyclopropyl group, and displays additional rocking motion. In contrast, the dynamics in the efavirenz cocrystals appear to be tamed, with the cyclopropyl group in the (efavirenz)(L-proline) cocrystal being the most constrained, and these constraints originating from a more favourable crystal packing in the cocrystals.

Graphical abstract: Taming the dynamics in a pharmaceutical by cocrystallization: investigating the impact of the coformer by solid-state NMR

Supplementary files

Article information

Article type
Paper
Submitted
13 Aug. 2021
Accepted
24 Aug. 2021
First published
02 Sept. 2021
This article is Open Access
Creative Commons BY license

CrystEngComm, 2021,23, 6859-6870

Taming the dynamics in a pharmaceutical by cocrystallization: investigating the impact of the coformer by solid-state NMR

P. M. J. Szell, J. R. Lewandowski, H. Blade, L. P. Hughes, S. O. Nilsson Lill and S. P. Brown, CrystEngComm, 2021, 23, 6859 DOI: 10.1039/D1CE01084K

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