Extension of Clausius-Clapeyron equation to predict hydrate stability at different temperatures. 1998

L R Chen, and D J Grant
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis 55455-0343, USA.

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.

UI MeSH Term Description Entries
D004355 Drug Stability The chemical and physical integrity of a pharmaceutical product. Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D013696 Temperature The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms. Temperatures
D013816 Thermodynamics A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed) Thermodynamic
D014867 Water A clear, odorless, tasteless liquid that is essential for most animal and plant life and is an excellent solvent for many substances. The chemical formula is hydrogen oxide (H2O). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Hydrogen Oxide
D017835 Nedocromil A pyranoquinolone derivative that inhibits activation of inflammatory cells which are associated with ASTHMA, including EOSINOPHILS; NEUTROPHILS; MACROPHAGES; MAST CELLS; MONOCYTES; AND PLATELETS. 9-Ethyl-6,9-dihydro-4,6-dioxo-10-propyl-4H-pyrano(3,2-g)quinoline-2,8-dicarboxylic acid,Alocril,Brionil,Cetimil,FPL-59002,Halamid,Irtan,Nedocromil Calcium,Nedocromil Sodium,Nedocromil, Calcium Salt (1:1),Nedocromil, Disodium Salt,Nedocromil, Disodium salt, Hydrate,Rapitil,Tilad,Tilade,Tilaire,Tilavist,Calcium, Nedocromil,FPL 59002,FPL59002,Sodium, Nedocromil

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