An Examination of Assumptions Underlying the First-Order Kinetic Model for Release of Water-Soluble Drugs from Dicalcium Phosphate Dihydrate Matrices

Abstract

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 geometry (2) was also reported. However, the rate constants for different geometry could not be predicted accurately by using the constants obtained for cylindrical tablets. In this work the assumptions regarding the surface area, porosity, and inertness of the drug toward the matrix have been tested using simple experimental designs and techniques such as porosimetry, electron microscopy, and differential scanning calorimetry. No interactions between the drug and the matrix were observed. The assumptions regarding porosity/void volume seemed to hold. Using water as a penetrant gave better estimate of porosities than those obtained using mercury. The assumption regarding surface area needs correction; however, a better alternative has not been proposed.