Use of Models in Determining Chemical Pharmaceutical Stability

Abstract

The area of chemical kinetics as it has been applied to the prediction of the stability of drugs in pharmaceutical formulations has been quite extensively discussed and reviewed during the past few years. In spite of this, a method has been developed which will, it is hoped, be especially useful in pharmaceutical product development work as distinguished from academic research studies in which the goals are to determine reaction rates or orders or to elucidate reaction mechanisms. The present method is based upon the construction of reference reaction paths which result logically when one considers the usual values of pertinent heats of reaction and considers normal shelf-life goals. Two results which have emerged from consideration of these paths are rules of thumb having a sound theoretical basis and a naturally arising logical assay schedule. The schedule arises because of the temperatures chosen for sample storage (RT, 37°, 45°, 60°, and 85°) and would change if another set of storage conditions was employed.