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Article Dans Une Revue Kona Powder and particles Année : 2011

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

Sébastien Teychené
Béatrice Biscans

Résumé

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.
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Dates et versions

hal-00801213 , version 1 (15-03-2013)

Identifiants

  • HAL Id : hal-00801213 , version 1
  • OATAO : 6043

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Sébastien Teychené, Béatrice Biscans. A Multiscale Approach for the Characterization and Crystallization of Eflucimibe Polymorphs: from Molecules to Particles. Kona Powder and particles, 2011, pp. 266-282. ⟨hal-00801213⟩
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