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MECANOSYNTHESE ET VITRIFICATION A L'ETAT SOLIDE D'ALLIAGES MOLECULAIRES

Abstract : This thesis deals with molecular alloys mechanosynthesis obtained by co-milling. The compounds studied are used as excipients in pharmaceutical industry. It concerns lactose, trehalose and mannitol. We show that co-milling of crystalline powders of trehalose/mannitol and of lactose/mannitol generate, for some composition range, homogeneous glass solutions. These studies show, from original way, the influence of milling temperature regard to glass transition temperature (Tg) on the nature of the final states obtained by milling : we have changed the glass transition temperature by changing the chemical composition of molecular alloys. The effect of milling on the pure compounds has also been studied. Ball milling of lactose and trehalose below their Tg induces a direct crystal - > glass transformation. Ball milling above Tg of mannitol ß, stable form, and of mannitol d, the most metastable form, induces a polymorphic transformation towards mannitol a, which is of intermediate stability. These results show that states obtained under ball milling are stationary states rather than thermodynamic equilibrium states. Moreover, our investigations permit to determine some specific properties of the systems studied which are not accessible from liquid states. We have characterised in details mutarotation of lactose. Binary phase diagrams trehalose/mannitol and lactose/mannitol are also proposed. All the results have been obtained by XRD, NMR, DSC and TGA experiments.
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Contributor : Vincent Caron <>
Submitted on : Thursday, February 7, 2008 - 3:51:06 PM
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Vincent Caron. MECANOSYNTHESE ET VITRIFICATION A L'ETAT SOLIDE D'ALLIAGES MOLECULAIRES. Sciences pharmaceutiques. Université des Sciences et Technologie de Lille - Lille I, 2006. Français. ⟨tel-00246474⟩

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