Details
| Original language | English |
|---|---|
| Pages (from-to) | 19103-19109 |
| Number of pages | 7 |
| Journal | Angewandte Chemie - International Edition |
| Volume | 58 |
| Issue number | 52 |
| Early online date | 26 Sept 2019 |
| Publication status | Published - 19 Dec 2019 |
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.
Keywords
- crystal growth, crystallization, nucleation, organic molecules
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Chemistry(all)
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In: Angewandte Chemie - International Edition, Vol. 58, No. 52, 19.12.2019, p. 19103-19109.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Liquid Metastable Precursors of Ibuprofen as Aqueous Nucleation Intermediates
AU - Wiedenbeck, Eduard
AU - Kovermann, Michael
AU - Gebauer, Denis
AU - Cölfen, Helmut
N1 - Funding Information: E.W. and H.C. thank the Deutsche Forschungsgemeinschaft (DFG) for financial support of this work (CO 194/21-1).
PY - 2019/12/19
Y1 - 2019/12/19
N2 - 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.
AB - 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.
KW - crystal growth
KW - crystallization
KW - nucleation
KW - organic molecules
UR - http://www.scopus.com/inward/record.url?scp=85074768006&partnerID=8YFLogxK
U2 - 10.1002/anie.201910986
DO - 10.1002/anie.201910986
M3 - Article
C2 - 31556970
AN - SCOPUS:85074768006
VL - 58
SP - 19103
EP - 19109
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
SN - 1433-7851
IS - 52
ER -