ArticleAngewandte Chemie (International ed. in English)2019
Liquid Metastable Precursors of Ibuprofen as Aqueous Nucleation Intermediates.
Article in Angewandte Chemie (International ed. in English), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Interfacial Nucleation Pathways Governing Polymorph Selection Revealed by Synchrotron-BasedJournal of the American Chemical Society · 2026Article
- Spectroscopic Evidence in Optical Absorption for the Formation and Transformation of Prenucleation Clusters of CdS Quantum Dots.ACS central science · 2026Article
- Promoting organic nucleation of diclofenac: hydrophobic interfacial interactions drive self-assembly.Chemical science · 2025Article
- Nonclassical Crystallization of the L‑Tartrate Salt of Cyamemazine.Crystal growth & design · 2025Article
- Guanine Crystallization by Particle Attachment.Journal of the American Chemical Society · 2025Article
- Chemically Specific Coherent Raman Imaging of Liquid-Liquid Phase Separation and Its Sequelae.Analytical chemistry · 2025Article
- Short-lived calcium carbonate precursors observed in situ via Bullet-dynamic nuclear polarization.Communications chemistry · 2024Article
- Exploring the Potential of Nonclassical Crystallization Pathways to Advance Cementitious Materials.Chemical reviews · 2024Review
- Nonclassical Crystallization and Core-Shell Structure Formation of Ibuprofen from Binary Solvent Solutions.Crystal growth & design · 2023Article
- Biodegradation of L-Valine Alkyl Ester Ibuprofenates by Bacterial Cultures.Materials (Basel, Switzerland) · 2021Article
- Continuum Crystallization Model Derived from Pharmaceutical Crystallization Mechanisms.ACS central science · 2021Article
- Article
- Non-classical crystallisation pathway directly observed for a pharmaceutical crystal via liquid phase electron microscopy.Scientific reports · 2020Article
- Liquid Metastable Precursors of Ibuprofen as Aqueous Nucleation Intermediates.Angewandte Chemie (International ed. in English) · 2019Article
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4 authors.
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Abstract
The nucleation mechanism of crystals of small organic molecules, postulated based on computer simulations, still lacks experimental evidence. In this study we designed an experimental approach to monitor the early stages of the crystallization of ibuprofen as a model system for small organic molecules. Ibuprofen undergoes liquid-liquid phase separation prior to nucleation. The binodal and spinodal limits of the corresponding liquid-liquid miscibility gap were analyzed and confirmed. An increase in viscosity sustains the kinetic stability of the dense liquid intermediate. Since the distances between ibuprofen molecules within the dense liquid phase are similar to those in the crystal forms, this dense liquid phase is identified as a precursor phase in the nucleation of ibuprofen, in which densification is followed by generation of structural order. This discovery may make it possible to enrich poorly soluble pharmaceuticals beyond classical solubility limitations in aqueous environments.
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