Stability assessment of pharmaceuticals by isothermal calorimetry: two component systems

isothermal calorimetry offers the potential to determine rapidly the stability of formulated pharmaceuticals because it is indifferent to physical form and sensitive enough to detect extremely small powers; ca. 50 nW at 25 degrees C. However, its use in this area is not widespread, principally because the power-time data obtained often comprise contributions from more than one process and are thus difficult to analyse quantitatively. In this work, we demonstrate how power-time data recorded for systems in which two components are degrading in parallel (in this case, binary mixtures of selected parabens) can be analysed using a kinetic-based model; the methodology allows the determination of the first-order rate constant and reaction enthalpy for each process, so long as one rate constant is at least twice the magnitude of the other. It was found that the reactions did not need to run to completion in order for the analysis to be successful; a minimum of 15 min of data were required for samples with one degrading component and a minimum of 4 h of data were required for samples with two degrading components. It was observed that the rate constants for paraben degradation in binary systems were significantly lower than expected. This was ascribed to the fact that the parabens degrade to a common product and is an important factor that should be accounted for when the two or more parabens are formulated together. (c) 2004 Elsevier B.V. All rights reserved.