The effect of polymer properties on direct compression and drug release from water-insoluble controlled release matrix tablets

Abstract

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 Kollidon(®) SR, Eudragit(®) 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 (T(g)), 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 T(g) (Kollidon(®) SR<Eudragit(®) 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-T(g) polymer (ethyl cellulose). However, release retardation was observed in the same order as matrix integrity (Eudragit(®) RS<ethyl cellulose<Kollidon(®) SR), as the high permeability was counteracted by PVP in case of Kollidon(®) SR. Therefore, the Tg and composition of a polymer need to be considered in polymer design and formulation of controlled-release matrix systems.

Keywords: Controlled release; Diprophylline (PubChem CID: 3182); Direct compression; Ethocel(®) Std. (PubChem CID: 24832091); Eudragit(®) RS (PubChem CID: 104931); Fumed silica (PubChem CID: 24261); Glass transition temperature; Magnesium stearate (PubChem CID: 11177); Matrix tablet; Percolation threshold; Polyvinyl pyrrolidone (PubChem CID: 6917); Water-insoluble polymers.