Impact of the polymer dispersity on the properties of curcumin/ polyvinylpyrrolidone amorphous solid dispersions

INTERNATIONAL JOURNAL OF PHARMACEUTICS(2024)

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摘要
Amorphous solid dispersions (ASD) are known to enhance the absorption of poorly water-soluble drugs. In this work we synthesise well-defined Polyvinylpyrrolidone (PVP) to establish the impact of dispersity and chain-end functionality on the physical properties of Curcumin (CUR)/PVP ASD. Thermodynamic characterisation of synthesised PVP emphasises a strong effect of the dispersity on the glass transition temperature (T-g), 50 degrees C higher for synthesised PVP than for commercial PVP K12 of same molar mass. This increase of T-g affects the thermodynamic properties of CUR/PVP ASD successfully formulated up to 70 wt% of CUR by milling or solvent evaporation. The evolution of both the T-g and CUR solubility values versus CUR content points out the development of fairly strong CUR-PVP interactions that strengthen the antiplasticising effect of PVP on the T-g of ASD. However, for ASD formulated with commercial PVP this effect is counterbalanced at low CUR content by a plasticising effect due to the shortest PVP chains. Moreover, the overlay of the phase and state diagrams highlights the strong impact of the polymer dispersity on the stability of CUR/PVP ASD. ASD formulated with low dispersity PVP are stable on larger temperature and concentration ranges than those formulated with PVP K12.
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关键词
Amorphous solid dispersions,Curcumin,Polyvinylpyrrolidone,Dispersity,Glass-transition,Solubility
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