Effect of water on the glass transition and properties of solid-state pharmaceutical formulations

• The aim of this thesis was to increase our knowledge of the glassy state and the glass transition phenomenon and to evaluate the effect of water on the glassy state. To accomplish this, investigations were focused on the amorphous sucrose-water (paper I, II, III), trehalose-water (paper I), maltodextrin-water (paper I), and lysozyme-sucrose-water (paper IV) systems.We studied temperature-induced and isothermal glass transition (I, II, III, IV), as well as the impact of water on the activation energy of the relaxation process (II). It has been shown that water undergoes glass transition with disaccharides, but in polysaccharides water dynamics is uncoupled from the polymer matrix. This results in differences in the water diffusion coefficient: water moves several orders of magnitude faster in the polymers than in disaccharides (I). Water reduces the activation energy of the relaxation process in the sucrose-water system (II). Attenuated water diffusion at sub-zero temperatures leads to a delay in water crystallization/melting in the sucrose-water system, which does not happen in a polysaccharide - water system (III). The Tg of the lysozyme-sucrose system increases with increasing lysozyme concentration, i.e., the DCp of the mixtures does not follow the prediction based on the properties of the pure components. Consequently, lysozyme does not modulate the glass transition of the sucrose matrix and the increase of the Tg of the mixtures is a result of the confinement of amorphous sucrose in the space between lysozyme molecules. The amorphous structure and unfolding of lysozyme in the presence of sucrose was investigated by DSC and SAXS. These data revealed an increase of the protein-protein distance upon addition of sucrose and upon heating, as a result of lysozyme unfolding (IV).

Nyckelord

glass transition

glass transition temperature

relaxation

sucrose

trehalose

maltodextrin

lysozyme

unfolding

hydration

solid-stae

sorption calorimetry

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