PERCOLATION EFFECTS IN MATRIX-TYPE CONTROLLED DRUG-RELEASE SYSTEMS

From experimental evidence it is well known that the bioavailability o f controlled release systems, i.e., the percentage of the dose absorbe d by the body, is often reduced compared to a corresponding dosage for m with immediate release. In the case of inert matrices, a water-solub le drug is embedded in a finely dispersed state in an insoluble carrie r material and released by diffusion. In the present work such systems are described by percolation theory. Based on a Bethe lattice model t he amount of drug substance 'trapped' in the matrices, which determine s the reduction of bioavailability, is calculated in a straight-forwar d way from the volume-to-volume ratio of drug and matrix material. To check the use of the model, matrix tablets are prepared with caffeine as a model drug and ethyl cellulose or hydrogenated castor oil as carr ier materials, and their drug release is determined in vitro. The expe rimental findings are in good agreement with the values predicted from the percolation model. The most pronounced reductions of bioavailabil ity are observed if the volume-to-volume ratio of drug and matrix subs tance is below a percolation threshold.