A number of factors controlling the rate of drug release from plastic matrices were investigated. It was found that the choice of plastic, weight of drug incorporated in matrix, solubility of drug used, matrix additives, and solvent could markedly affect the release rate. The changes in experimental drug release behavior as a function of these variables were determined and compared to the ex ected results determined from theory. The matrix tortuosity factor was studied by caching drug from tablet and then resaturating the porous matrix with a 5 per cent sodium salicylate solution. The release rate of sodium salicylate from these resaturated matrices were determined, and relative tortuosities were calculated.
ECENTLY, Higuchi proposed that the rate of R release of drug from one surface of an insoluble matrix would be governed by the following relationship (1) :
where Q is the grams of drug released per unit area of surface a t time, t, D is the diffusion coefficient of drug in release medium, e is the porosity of the matrix, C, is the solubility of drug in release medium, 7 is the tortuosity of the matrix, and A is the concentration of drug in tablet expressed as Gm./ml. This report will discuss the results of a preliminary investigation of its applicability to the study of release rates of drugs from matrices. The importance of this study need not be emphasized as this has been adequately discussed in recent publications (2-4). Theoretically, any variable in the equation could be utilized to govern the rate of release, providing its variability can be controlled. Before this can be accomplished, however, there must be available a method by which each variable can be measured.
The equation predicts a straight-line relationship if the amount of drug released per unit area is plotted versus the square root of time. A series of experiments would be designed in such a way as to vary only one variable in a predetermined manner and hopefully keep all other variables constant. The slopes of the various curves obtained would be compared, and in this way the effect of the controlled variation on the rate of release could be determined, This result would then be compared with the theoretical effect predicted by the equation.
The method of attack was simple.