Non-classical crystallisation pathway directly observed for a pharmaceutical crystal via liquid phase electron microscopy.

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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Cookman J,Hamilton V,Hall SR,Bangert U

doi

10.1038/s41598-020-75937-2

subject

Has Abstract

pub_date

2020-11-05 00:00:00

pages

19156

issue

1

issn

2045-2322

pii

10.1038/s41598-020-75937-2

journal_volume

10

pub_type

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