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- W2894928426 abstract "Amorphous pharmaceuticals (excipients and active ingredients) are considered as one of the most promising approach to overcome the poor water solubility issue related to many drug molecules. Preparing poorly soluble drugs in the amorphous state is thus becoming an essential strategy for incorporating drugs into highly effective dosage forms. Recent developments have highlighted the need of a better understanding of the impact of preparation pathway onto the resulting amorphous solids. The aim of this thesis is to contribute to a rational knowledge of the differences in the amorphous state generated by two distinct preparation pathways: quenching from the melt and high-energy milling. Physico-chemical properties of the amorphous materials were studied using a set of analytical methods (structural, thermal and spectroscopic) coupled to quantum DFT calculations. It was demonstrated for two compounds of pharmaceutical interest that depending on the preparation methods, properties such as physical stability and crystallization kinetics might differ, leading to distinct behaviors upon storage. Melt-quenched states have been found to possess a good stability over time, while milled ones exhibit a lower stability resulting in an easier tendency toward crystallization. Moreover, beyond the glass transition temperature, it was outstanding to note that all discrepancies in physico-chemical properties are suppressed. Our findings indicate also that the propensity of both inspected molecular compounds to be amorphized rises as milling temperature decreases. This thesis also provides new insights to elaborate adequate stabilization protocols for amorphous pharmaceuticals." @default.
- W2894928426 created "2018-10-12" @default.
- W2894928426 creator A5037486240 @default.
- W2894928426 date "2016-12-02" @default.
- W2894928426 modified "2023-09-25" @default.
- W2894928426 title "Molecular Mobility, Crystallization Mechanisms and Physical Stability of Amorphous Pharmaceutical Compounds:Impact of Preparation Pathways" @default.
- W2894928426 hasPublicationYear "2016" @default.
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