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A Multiscale Approach for the Characterization and Crystallization of Eflucimibe Polymorphs: from Molecules to Particles

Teychené, Sébastien and Biscans, Béatrice A Multiscale Approach for the Characterization and Crystallization of Eflucimibe Polymorphs: from Molecules to Particles. (2011) Kona Powder and particles (n° 29). pp. 266-282. ISSN 0288-4534

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Official URL: http://www.kona.or.jp/

Abstract

We present in this paper a generic multiscale methodology for the characterization and crystallization of eflucimibe polymorphs. The various characterization techniques used have shown that eflucimibe polymorphism is due to a conformational change of the molecule in the crystal lattice. In addition, the two polymorphs are monotropically related in the temperature range tested and have similar structures and properties (ie. interfacial tension and solubility). Consequently, it was found that for a wide range of operating conditions, the polymorphs may crystallize concomitantly. Induction time measurements and metstable zone width determination allow to infer the origin of the concomitant appearance of the polymorphs. A predominance diagram has been established which allows to perfectly control the crystallization of the desired polymorph. However, even if the stable form can be produced in a reliable way, the crystal suspension went toward a very structured gel-like network which limits the extrapolation process. Based on microscopic observation of the crystallization events performed in a microfluidic crystallizer, we propose a range of operating conditions suitable for the production of the stable form with the desired handling properties.

Item Type:Article
Additional Information:Thanks to Hosokawa Powder Technology Foundation editor. The definitive version is available at http://www.kona.or.jp The original PDF of the article can be found at : http://www.kona.or.jp/html/about/index2011.html
HAL Id:hal-00801213
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:French research institutions > Centre National de la Recherche Scientifique - CNRS (FRANCE)
Université de Toulouse > Institut National Polytechnique de Toulouse - INPT (FRANCE)
Université de Toulouse > Université Toulouse III - Paul Sabatier - UPS (FRANCE)
Laboratory name:
Laboratoire de Génie Chimique - LGC (Toulouse, France) - Génie des Interfaces & Milieux Divisés (GIMD)
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Deposited By: Audrey LEFEVRE
Deposited On:14 Jan 2013 14:50

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