The objectives of this study were to verify theoretically and experimentally that the Clausius-Clapeyron equation can be applied to a hydrate system, and to use this equation to predict the equilibrium water activity for a hydrate pair existing in equilibrium at different temperatures for the determination of the ranges of hydrate stability. The Clausius-Clapeyron equation was derived for hydrate systems by assuming (a) the higher and the lower hydrates exist in equilibrium with water vapor as three pure phases; and (b) the overall volume change involved in this equilibrium process is approximated by the volume of the released water vapor, which behaves ideally. The equilibrium water vapor pressure at different temperatures for the nedocromil sodium monohydrate and trihydrate system was determined dynamically using a thermogravimetric analyzer with an attached water vapor delivery system. The enthalpy of dehydration obtained by applying the Clausius-Clapeyron equation to the experimentally determined equilibrium water vapor pressures is in fair agreement with the enthalpy of dehydration derived from differential scanning calorimetry (13.7 +/- 0.6 kcal/mol of water loss, n = 5), indicating that the Clausius-Clapeyron equation can indeed be applied to organic hydrate systems. The application of the Clausius-Clapeyron equation to predict the hydrate stability under various conditions is also discussed.
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