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.
Use of isothermal heat-conduction microcalorimetry (IHCMC) for the evaluation of synthetic biomaterials.
Isothermal heat-conduction microcalorimetry (IHCMC) allows measurement of extremely small rates of heat flow-on the order of 0.1 microwatt. This provides, for example, the ability to directly observe-and quantitate in a few days-rates of degradation as low as 1% per year at body temperature, in solid material samples of a few grams. Also, one method of IHCMC data analysis allows direct determination of the reaction-rate constant at the temperature of interest, thereby avoiding possible errors due to rate mechanism changes with temperature, an issue that needs to be considered when the Arrhenius method is used. IHCMC can also be used to measure transient phenomena, such as heat of adsorption, and initial metabolic responses of cellular entities to biomaterials. The purposes of this review article are to (a) explain the basic principles, attractive features, limitations, and methods of IHCMC; (b) describe biomaterials applications to date--including studies of the stability of ultra-high-molecular-weight polyethylene and implant-grade calcium sulfate, setting reactions of dental adhesives, and macrophage response to biomaterial particles; (c) provide a discussion of issues and concerns that should be addressed in order to maximize the utility of IHCMC in biomaterials studies; and (d) suggest a number of possible future biomaterials applications for this technique.
Simple g(α) non dependent method to solve the kinetic parameters by isothermal thermogravimetry
Abstract In a previous work [1], we presented the demonstration of the relationship between the activation energy value and the square of the temperature, and the slope of a non-isothermal thermogram. We present in this work, following similar arguments, a coherent demonstration with conclusions, that the relationship between Ea and the square of the temperature occurs under isothermal conditions, too. It can be demonstrated too, that Ea depends on the relative slope of at least two isothermal runs. We conclude that there is complete independence of the Ea and the g(α) value for the isothermal conditions. From the results, a simple graphical-numerical method, based on isothermal thermogravimetry, is proposed to solve and calculate the kinetic parameters Ea, K(T), and K0 and the kinetic model in a very easy and accurate way.