Matrix type controlled release systems II. Percolation effects in non-swellable matrices

Abstract

Abstract Two types of non-swellable matrix tablets were prepared by compressing binary mixtures of the water-soluble model drug caffeine with either ethyl cellulose (EC) as an inert, or hydrogenated castor oil (HCO) as a lipophilic matrix-forming excipient. The drug content in the tablets was varied from 10% to 95% (weight/weight). The drug release was measured from both flat sides of the tablets separately by a rotating-disk method. At the same drug loading, the tablet side having faced the upper punch during single-punch compaction showed a slower release rate than the opposite side, which can probably be attributed to differences in compaction pressure as well as in drug distribution between upper and lower side. Additionally, the drug release from the entire tablets was determined in flow-through cell. From the dissolution data the percolation thresholds of the matrix systems were calculated according to a previously published method. The lower percolation threshold, expressed as total porosity of the completely leached matrix, ranged between 0.30 and 0.36, which can be explained by site percolation on a three-dimensional lattice of isomeric particles of drug and matrix substance. The upper percolation threshold, expressed as critical volume fraction of the matrix substance, was about 0.30 for the EC-matrices, but only 0.06 for the HCO-matrices. The latter shift to a very low percolation threshold may be attributed to the different particle sizes of matrix and active substance. A comparison of the drug release profiles determined in the flow-through cell shows the different behaviour of the two matrices with increasing drug loadings. Based on the concepts of percolation theory, the reasonable range of mixing ratios of drug and matrix substance yielding an optimal dissolution behaviour has to be evaluated, offering the possibility of a more rational dosage form design.