Author:
Cookman J.,Hamilton V.,Hall S. R.,Bangert U.
Abstract
Abstract
Non-classical crystallisation (NCC) pathways are widely accepted, however there is conflicting evidence regarding the intermediate stages of crystallisation, how they manifest and further develop into crystals. Evidence from direct observations is especially lacking for small organic molecules, as distinguishing these low-electron dense entities from their similar liquid-phase surroundings presents signal-to-noise ratio and contrast challenges. Here, Liquid Phase Electron Microscopy (LPEM) captures the intermediate pre-crystalline stages of a small organic molecule, flufenamic acid (FFA), a common pharmaceutical. High temporospatial imaging of FFA in its native environment, an organic solvent, suggests that in this system a Pre-Nucleation Cluster (PNC) pathway is followed by features exhibiting two-step nucleation. This work adds to the growing body of evidence that suggests nucleation pathways are likely an amalgamation of multiple existing non-classical theories and highlights the need for the direct evidence presented by in situ techniques such as LPEM.
Funder
Horizon 2020 Framework Programme
Engineering and Physical Sciences Research Council
Publisher
Springer Science and Business Media LLC
Reference38 articles.
1. Walter, M. W. Structure-based design of agrochemicals. Nat. Prod. Rep. 19, 278–291 (2002).
2. Jena, D., Banerjee, K. & Xing, G. H. 2D crystal semiconductors: Intimate contacts. Nat. Mater. 13, 1076–1078 (2014).
3. Sunagawa, I. Characteristics of crystal growth in nature as seen from the morphology of mineral crystals. Bull. Mineral. 104, 81–87 (1981).
4. Johan Wouters, Q. L. Pharmaceutical salts and co-crystals. Pharmac. Salts Co-cryst.
https://doi.org/10.1039/9781849733502
(2011).
5. Pharma Industry Weighs in on Continuous Manufacturing.
https://www.dcatvci.org/6007-pharma-industry-weighs-in-on-continuous-manufacturing
.
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