THE ROLE OF THE DRUG EXCIPIENT PARTICLE-SIZE RATIO IN THE PERCOLATIONMODEL FOR TABLETS/

Purpose. In previous papers, a linear relationship between drug partic le size and drug percolation threshold was found in inert matrix table ts. The main objectives of the present work are: to study the influenc e of the excipient particle size on the drug percolation threshold and to investigate if the change in the drug percolation threshold is due either to the absolute or to the relative drug particle size. Methods . Matrix tablets have been prepared using KCI (7 different particle si ze fractions) as a drug model and Eudragit(R) RS-PM (4 granulommetric fractions) as matrix forming material. In vitro release assays were ca rried out on the 66 lots of tablets. The drug percolation thresholds w ere estimated following the method of Bonny and Leuenberger. Results, The particle size of the excipient has shown an opposite effect to the drug size on the drug percolation threshold. Nevertheless, the influe nce of drug and excipient sizes on the drug percolation threshold are of the same magnitude. Conclusions. The drug percolation threshold dep ends linearly on the relative drug particle size. This finding is in a greement with percolation theory and can facilitate the use of the per colation threshold as a preformulation parameter to improve the pharma ceutical dosage forms design.