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Free keywords:
Thermal analysis; Phase behavior; Polymorphism
Abstract:
Thermodynamic data are crucial for designing any chemical process. With regard to crystallization, solubility phase diagrams provide the regions and experimental conditions for producing pure compounds. Solubilities can be extracted from various reference sources. However, solubilities of new pharmaceuticals or fine chemicals in different and mixed solvents are usually unknown. The determination of these data by means of classical techniques is connected with significant time and substance consumption. Moreover, for complex multicomponent systems an appropriate analytical procedure has to be developed. Therefore innovative methods reducing the experimental efforts are of special interest. The contribution to be presented is concerned with the validation of the applicability of a polythermal calorimetric approach for solubility measurements. The method is based on the heat absorbed or released by dissolution of the solid in a solvent. The thermal effect observed is described with a model resulting from mass and enthalpy balances as already shown [1]. It can be used on the one hand, to calculate thermograms by means of thermodynamic parameters and on the other hand, to convert the experimental data into solubility curves. Two devices are applied for the measurements a Calvet-type DSC (DSC 111, Setaram) and a twin-type reaction calorimeter (DRC, Setaram). Relevant pharmaceuticals, mandelic acid, glycine and xylose in different solvents are systems under study. In addition to the calorimetric experiments classical isothermal solubility determinations with phase separation and analysis are undertaken. On this basis, a detailed comparison between both techniques is given and the advantages and limitations of the calorimetric method are derived.
[1] Sapoundjiev, D., Lorenz, H., Seidel-Morgenstern, A.: Calorimetry as a tool for solubility determination theoretical and experimental study, Proceedings 10th International Workshop on Industrial Crystallization (BIWIC 2003), Rouen (France), 4.09.-5.09.2003, pp. 264-272.
