Solid-State Stability Testing of Drugs by Isothermal Calorimetry
A new technique has been developed to calculate rapidly the solid-state room-temperature degradation rate of drugs and drug candidates. The technique utilizes measurements of the initial rate of heat output at several elevated temperatures by isothermal calorimetry and the degradation rate of the compound determined at a single elevated temperature by chromatography. The activation energies and degradation rates at 25°C calculated by conventional methods and by isothermal calorimetry are compared and discussed. The compounds studied were phenytoin, triamterene, digoxin, tetracycline, theophylline, diltiazem, and several proprietary ICI compounds.
Kinetics of Drug Decomposition by Heat Conduction Calorimetry
The application of heat conduction calorimetry to the determination of decomposition mechanisms and rates for drugs is shown to be a rapid and generally useful method. The application of the method to determine the nature of the decomposition reaction, sources of systematic errors in the method, the equations relating the calorimetric signal to the kinetics of the reaction, and some examples of results are presented and discussed.
Definition of Rate Constant and Activation Energy in Solid State Reactions
DISLOCATIONS in alkali halide crystals doped with silver ions can be ‘decorated’ by a hydrogen treatment, which causes reduction and subsequent precipitation of silver1. In the course of work on the kinetics of this solid state reaction, the problem arose of deducing the reaction constant and the activation energy without exact knowledge of the reaction mechanism, which is rarely discussed in the literature.