Kinetics and mechanism of polymorphic transformation of sorbitol under mechanical milling.

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. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Anthony Dupont, Mathieu Guerain, Florence Danède, Laurent Paccou, Yannick Guinet, Alain Hédoux, Jean-François Willart. Kinetics and mechanism of polymorphic transformation of sorbitol under mechanical milling. International journal of pharmaceutics. 2020 Nov 30;590:119902

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PMID: 32980510

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