Opening Pandora’s Box: Chirality, Polymorphism, and Stoichiometric Diversity in Flurbiprofen/Proline Cocrystals

Natalia Tumanova, Nikolay Tumanov, Koen Robeyns, Franziska Fischer, Luca Fusaro, Fabrice Morelle, Voraksmy Ban, Geoffroy Hautier, Yaroslav Filinchuk, Johan Wouters, Tom Leyssens, Franziska Emmerling

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

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.
langue originaleAnglais
Pages (de - à)954-961
Nombre de pages8
journalCrystal Growth & Design
Volume18
Numéro de publication2
Les DOIs
étatPublié - 4 janv. 2018

Empreinte digitale

Flurbiprofen
Chirality
polymorphism
Ball milling
grinding
Polymorphism
chirality
Proline
boxes
balls
Liquids
liquids
Drug products
Reaction rates
Density functional theory
reaction kinetics
Crystal structure
density functional theory
X ray diffraction
Crystals

Citer ceci

Tumanova, Natalia ; Tumanov, Nikolay ; Robeyns, Koen ; Fischer, Franziska ; Fusaro, Luca ; Morelle, Fabrice ; Ban, Voraksmy ; Hautier, Geoffroy ; Filinchuk, Yaroslav ; Wouters, Johan ; Leyssens, Tom ; Emmerling, Franziska. / Opening Pandora’s Box : Chirality, Polymorphism, and Stoichiometric Diversity in Flurbiprofen/Proline Cocrystals. Dans: Crystal Growth & Design. 2018 ; Vol 18, Numéro 2. p. 954-961.
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title = "Opening Pandora’s Box: Chirality, Polymorphism, and Stoichiometric Diversity in Flurbiprofen/Proline Cocrystals",
abstract = "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.",
author = "Natalia Tumanova and Nikolay Tumanov and Koen Robeyns and Franziska Fischer and Luca Fusaro and Fabrice Morelle and Voraksmy Ban and Geoffroy Hautier and Yaroslav Filinchuk and Johan Wouters and Tom Leyssens and Franziska Emmerling",
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Tumanova, N, Tumanov, N, Robeyns, K, Fischer, F, Fusaro, L, Morelle, F, Ban, V, Hautier, G, Filinchuk, Y, Wouters, J, Leyssens, T & Emmerling, F 2018, 'Opening Pandora’s Box: Chirality, Polymorphism, and Stoichiometric Diversity in Flurbiprofen/Proline Cocrystals', Crystal Growth & Design, VOL. 18, Numéro 2, p. 954-961. https://doi.org/10.1021/acs.cgd.7b01436

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.

Dans: Crystal Growth & Design, Vol 18, Numéro 2, 04.01.2018, p. 954-961.

Résultats de recherche: Contribution à un journal/une revueArticle

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

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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.

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