Continuum Crystallization Model Derived from Pharmaceutical Crystallization Mechanisms
| Autor: | Lothar Houben, Eduard Wiedenbeck, Idan Biran, Boris Rybtchinski, Helmut Cölfen, Yael Tsarfati |
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| Rok vydání: | 2021 |
| Předmět: |
Materials science
010405 organic chemistry General Chemical Engineering Continuum (design consultancy) General Chemistry 010402 general chemistry 01 natural sciences 0104 chemical sciences law.invention Organic molecules Amorphous solid Chemistry Transmission electron microscopy law Chemical physics ddc:540 Crystals Imaging Crystallization Crystal structure Order Low density QD1-999 Research Article |
| Zdroj: | ACS Central Science ACS Central Science, Vol 7, Iss 5, Pp 900-908 (2021) |
| ISSN: | 2374-7951 2374-7943 |
| DOI: | 10.1021/acscentsci.1c00254 |
| Popis: | The crystallization mechanisms of organic molecules in solution are not well-understood. The mechanistic scenarios where crystalline order evolves directly from the molecularly dissolved state (“classical”) and from initially formed amorphous intermediates (“nonclassical”) are suggested and debated. Here, we studied crystallization mechanisms of two widely used analgesics, ibuprofen (IbuH) and etoricoxib (ETO), using direct cryogenic transmission electron microscopy (cryo-TEM) imaging. In the IbuH case, parallel crystallization pathways involved diverse phases of high and low density, in which the instantaneous formation of final crystalline order was observed. ETO crystallization started from well-defined round-shaped amorphous intermediates that gradually evolved into crystals. This mechanistic diversity is rationalized by introducing a continuum crystallization paradigm: order evolution depends on ordering in the initially formed intermediates and efficiency of molecular rearrangements within them, and there is a continuum of states related to the initial order and rearrangement rates. This model provides a unified view of crystallization mechanisms, encompassing classical and nonclassical pictures. Continuum crystallization model: the order evolution pattern depends on ordering in the initially formed intermediates and efficiency of molecular rearrangements within them. |
| Databáze: | OpenAIRE |
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