Kinetics of drug release from solid matrices: effect of compaction pressure

Abstract

Measurements have been made of the compactibility of drug/polymers and their mixtures with directly compressible excipients, and of the tensile strength of the solid matrices produced either by fusion or by physical mixing. It was found that at a relatively low compaction force a plateau is observed without appreciable change in tensile strength at greater pressure. The influence of compression force on dissolution rate in both the initial release phase and the matrix-controlled diffusion phase was determined. It was shown that dissolution of a drug from insoluble and partially soluble matrices follows the Higuchi square-root equation. Release profiles of solid matrices produced from isotropic dispersions obtained by fusion are susceptible to compression force in both the initial and terminal phases with significant differences in the slopes of square-root plots. Furthermore, drug release from physical mixtures of directly compressed formulations is not affected by an increase in compression force. There is no significant change in the slopes of release profiles which have consistently higher correlation coefficients.