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Kinetics and mechanism of polymorphic transformation of sorbitol under mechanical milling

Abstract : In this paper, we present a kinetic investigation of the polymorphic transformation γ → α of sorbitol under milling in the objective to identify the microscopic mechanisms that govern this type of solid-state transformation. The milling was performed with a high energy planetary mill and the milled material was analysed by DSC, PXRD and Raman spectrometry. The transformation kinetics was found to be sigmoidal with a noticeable incubation time. Moreover, this incubation time was shown to shorten rapidly when seeding the initial form γ with the final form α. The origin of the incubation period and its evolution upon seeding are puzzling as polymorphic transformations induced by milling are not expected to occur through a nucleation and growth process. To explain these puzzling kinetic features, we propose a two-step transformation mechanism involving local amorphisations due to the mechanical impacts, immediately followed by rapid recrystallizations of the amorphized fractions. The key point of the mechanism is that recrystallizations are oriented towards the forms γ or α, depending on the crystalline form of neighbouring crystallites. This mechanism has been validated by numerical simulations which were able to reproduce all the experimental kinetic features of the polymorphic transformation (kinetic law and effects of seeding) upon milling.
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Soumis le : mardi 13 octobre 2020 - 12:17:29
Dernière modification le : mardi 20 octobre 2020 - 09:48:01

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Anthony Dupont, Mathieu Guerain, Florence Danede, Laurent Paccou, Yannick Guinet, et al.. Kinetics and mechanism of polymorphic transformation of sorbitol under mechanical milling. International Journal of Pharmaceutics, Elsevier, 2020, International Journal of Pharmaceutics, 590, pp.119902. ⟨10.1016/j.ijpharm.2020.119902⟩. ⟨hal-02965510⟩

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