Application of a new mathematical method for the estimation of the mean surface area to calculate the percolation threshold of lobenzarit dissodium salt in controlled release matrices

Abstract

One of the practical handicaps for the application of the percolation theory to estimate the percolation threshold of drugs in controlled release systems is the fact that the dissolution studies must be carried out so that only one surface of the tablet is exposed to the dissolution medium. The aim of this work is to estimate the percolation threshold of the antiarthritic drug lobenzarit dissodium (LBD) in inert matrices prepared with the excipients Ethocel® 100 and Eudragit® RS-PO (10-75% w/w). Release assays were performed using the paddle method. The whole surface of the tablets was exposed to the dissolution medium. For the first time, a new mathematical method is developed to transform the amount of drug released in amount released per surface area in order to calculate the percolation thershold of LBD. The mathematical method proposed allows to calculate, using a new equation, the evolution of the mean surface area (O(t)). The new method was validated and three novel results were achieved: A constant value of (O (t)) at critical time (θ) in the matrices (O (θ)=1.272 cm2); a linear relationship between initial surface area (O(0)) and critical time; and a linear relationship between O(t) and time. Employing the values of O (t), it was possible to calculate for the first time, the percolation threshold (pc1) for LBD in Ethocel® 100 (pc1=0. 280±0.102) and Eudragit® RS-PO (pc1=0.344±0.07) matrices. © 2004 Pharmaceutical Society of Japan.