Chemical stability study of the solid state

There have been many attempts to derive a comprehensive model for solid state reactions, however, no completely satisfactory method has been applied universally. This probably reflects the complex nature of a solid state reaction. This problem must be addressed if general predictions are to be made about the long-term stability of drugs in the solid state. 

The equations for various solid state degradation models, (p) and (q) are fitting parameters related to the mechanism of reaction. a,/2 is the half life of the reaction. 

Equations such as the general Ng equation (Equation (10)) are commonly used to model solid state reactions, where the rate of reaction is plotted against the fraction of degradation. 

Isothermal microcalorimetry has proved useful for the study of solid state reactions giving rise to information about the reaction model and hence the reaction mechanism [65,66]. Additional studies have been performed where a satisfactory outcome of the data analysis was achieved [67-71]. 

Reaction kinetics from DSC, DTA or TGA, have been used to examine the stability of a limited number of pharmaceutical materials. Various models have been used including the Power Law, Avarami-Erofeev and Prout-Tomkins models [72]. These methods are also based on the Kissinger [73], ASTME 698 [74] or Ozawa [75] methods [8]. Most frequently, they have been applied to the dehydration of various materials such as theophylline monohydrate [76], phenobarbitone monohydrate or hemihydrate [77], phenylbutazone [78], oxazepam [23] and trazodone tetrahydrate [79]. The uses are limited for pharmaceutical systems, not least because dehydration is particle size dependent. Thermal analysis, especially DSC, DTA and TG, has been used outside the pharmaceutical area in the prediction of reaction kinetics as described elsewhere in this handbook. Methods used include those by Borchart and Daniels [80], Kissinger [73], Freeman and Carroll [81] and Flynn and Wall [82]. Although these techniques are well established and, if used properly, can give pertinent information, their use in pharmaceutical arenas is restricted to dehydration and decomposition. 

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