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The objective of this study was to identify and evaluate key polymer properties affecting direct compression and drug release from water-insoluble matrices. Commonly used polymers, such as Kollidon1 SR, Eudragit1 RS and ethyl cellulose, were characterized, formulated into tablets and compared with regard to their properties in dry and wet state. A similar site percolation threshold of 65% v/v was found for all polymers in dry state. Key parameters influencing polymer compactibility were the surface properties and the glass transition temperature (Tg), affecting polymer elasticity and particle size-dependent binding. The important properties observed in dry state also governed matrix characteristics and therefore drug release in wet state. A low Tg (Kollidon1 SR < Eudragit1 RS) decreased the percolation threshold, particle size effect and tortuosity, but increased permeability and sensitivity to heat/humidity treatment. Hence, lower permeability and higher stability are benefits of a high-Tg polymer (ethyl cellulose). However, release retardation was observed in the same order as matrix integrity (Eudragit1 RS < ethyl cellulose < Kollidon1 SR), as the high permeability was counteracted by PVP in case of Kollidon1 SR. Therefore, the Tg and composition of a polymer need to be considered in polymer design and formulation of controlled-release matrix systems.

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