RELATIONSHIP BETWEEN DRUG PERCOLATION-THRESHOLD AND PARTICLE-SIZE IN MATRIX TABLETS

Purpose. Since a previous qualitative study carried out by us showed t he existence of an important influence of the particle size on the per colation thresholds and taking into account that the existing theoreti cal models can only provide qualitative explanation to this influence, the purpose of this work is to carry out the first quantitative study of the influence of the particle size over the drug percolation thres holds. Methods. Matrix tablets have been elaborated using potassium ch loride as drug model and Eudragit RS-PM as matrix forming material. Fi ve different KCI particle size fractions have been employed whereas th e Eudragit(R) RS-PM particle size was kept constant. In-vitro release assays were carried out for all the elaborated lots. The drug percolat ion thresholds were estimated following the method proposed by Bonny a nd Leuenberger. Results. A linear relationship has been found between the drug particle size and the corresponding drug percolation threshol d. Conclusions. This finding confirms the results previously obtained in our qualitative study and has important repercussions in the design of pharmaceutical solid dosage forms. If this linear behaviour is gen eral, the percolation threshold can soon become a useful preformulatio n parameter.