ArticleScientific reports2020
Non-classical crystallisation pathway directly observed for a pharmaceutical crystal via liquid phase electron microscopy.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Nonclassical Crystallization of the L‑Tartrate Salt of Cyamemazine.Crystal growth & design · 2025Article
- Rationalizing the Influence of Solvent on the Nucleation of Griseofulvin through Classical and Nonclassical Pathways.Crystal growth & design · 2025Article
- The Influence of Ionizing Radiation on Quantification for In Situ and Operando Liquid-Phase Electron Microscopy.Advanced materials (Deerfield Beach, Fla.) · 2025Review
- Tracking Prenucleation Molecular Clustering of Salicylamide in Organic Solvents.Crystal growth & design · 2024Article
- Nonclassical Crystallization and Core-Shell Structure Formation of Ibuprofen from Binary Solvent Solutions.Crystal growth & design · 2023Article
- Laser-induced convection shifts size distributions in nanoparticle tracking analysis.Nanoscale advances · 2021Article
- Pure Curcumin Spherulites from Impure SolutionsACS omega · 2021Article
- Continuum Crystallization Model Derived from Pharmaceutical Crystallization Mechanisms.ACS central science · 2021Article
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Authors and funding
4 authors.
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No grant is acknowledged in the PubMed record.
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.
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