AN EXAMINATION OF ASSUMPTIONS UNDERLYING THE FIRST-ORDER KINETIC-MODEL FOR RELEASE OF WATER-SOLUBLE DRUGS FROM DICALCIUM PHOSPHATE DIHYDRATE MATRICES

It has been shown that the release of highly water-soluble drugs from compressed dicalcium phosphate dihydrate matrices follows first-order kinetics (1). Good correlation between the rate constant and tablet ge ometry (2) was also reported. However, the rate constants for differen t geometry could not be predicted accurately by using the constants ob tained for cylindrical tablets. In this work the assumptions regarding the surface area, porosity, and inertness of the drug toward the matr ix have been tested using simple experimental designs and techniques s uch as porosimetry, electron microscopy, and differential scanning cal orimetry. No interactions between the drug and the matrix were observe d. The assumptions regarding porosity/void volume seemed to hold. Usin g water as a penetrant gave better estimate of porosities than those o btained using mercury, The assumption regarding surface area needs cor rection; however, a better alternative has not been proposed.