Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 954-961 |
| Number of pages | 8 |
| Journal | Crystal Growth & Design |
| Volume | 18 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 4 Jan 2018 |
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Opening Pandora’s Box : Chirality, Polymorphism, and Stoichiometric Diversity in Flurbiprofen/Proline Cocrystals. / Tumanova, Natalia; Tumanov, Nikolay; Robeyns, Koen; Fischer, Franziska; Fusaro, Luca; Morelle, Fabrice; Ban, Voraksmy; Hautier, Geoffroy; Filinchuk, Yaroslav; Wouters, Johan; Leyssens, Tom; Emmerling, Franziska.
In: Crystal Growth & Design, Vol. 18, No. 2, 04.01.2018, p. 954-961.Research output: Contribution to journal › Article
TY - JOUR
T1 - Opening Pandora’s Box
T2 - Chirality, Polymorphism, and Stoichiometric Diversity in Flurbiprofen/Proline Cocrystals
AU - Tumanova, Natalia
AU - Tumanov, Nikolay
AU - Robeyns, Koen
AU - Fischer, Franziska
AU - Fusaro, Luca
AU - Morelle, Fabrice
AU - Ban, Voraksmy
AU - Hautier, Geoffroy
AU - Filinchuk, Yaroslav
AU - Wouters, Johan
AU - Leyssens, Tom
AU - Emmerling, Franziska
PY - 2018/1/4
Y1 - 2018/1/4
N2 - Proline has been widely used for various cocrystallization applications, including pharmaceutical cocrystals. Combining enantiopure and racemic flurbiprofen and proline, we discovered 18 new crystal structures. Liquid-assisted grinding proved highly efficient to explore all the variety of crystal forms. A unique combination of state-of-the-art characterization techniques, comprising variable temperature in situ X-ray diffraction and in situ ball-milling, along with other physicochemical methods and density functional theory calculations, was indispensable for identifying all the phases. Analyzing the results of in situ ball-milling, we established a stepwise mechanism for the formation of several 1:1 cocrystals via an intermediate 2:1 phase. The nature of the solvent in liquid-assisted grinding was found to significantly affect the reaction rate and, in some cases, the reaction pathway.
AB - Proline has been widely used for various cocrystallization applications, including pharmaceutical cocrystals. Combining enantiopure and racemic flurbiprofen and proline, we discovered 18 new crystal structures. Liquid-assisted grinding proved highly efficient to explore all the variety of crystal forms. A unique combination of state-of-the-art characterization techniques, comprising variable temperature in situ X-ray diffraction and in situ ball-milling, along with other physicochemical methods and density functional theory calculations, was indispensable for identifying all the phases. Analyzing the results of in situ ball-milling, we established a stepwise mechanism for the formation of several 1:1 cocrystals via an intermediate 2:1 phase. The nature of the solvent in liquid-assisted grinding was found to significantly affect the reaction rate and, in some cases, the reaction pathway.
UR - http://www.scopus.com/inward/record.url?scp=85041915775&partnerID=8YFLogxK
U2 - 10.1021/acs.cgd.7b01436
DO - 10.1021/acs.cgd.7b01436
M3 - Article
VL - 18
SP - 954
EP - 961
JO - Crystal Growth and Design
JF - Crystal Growth and Design
SN - 1528-7483
IS - 2
ER -