Crystallization of probucol from solution and the glassy state

Crystallization of probucol (PBL) from both solution and glassy solid state was investigated. In the crystallization study from solution, six solvents and three methods, i.e., evaporation, addition of a poor solvent, and cooling on ice, were used to obtain various crystal forms. In addition to common two crystal forms (forms I and II), two further forms (forms III and cyclohexane-solvate) were found in this study, and their thermodynamic relationships were determined. Forms I and II are likely to be enantiotropically related with thermodynamic transition temperature below 5 °C. Isothermal crystallization studies revealed that PBL glass initially crystallized into form III between 25 and 50 °C, and then transformed to form I. The isothermal crystallization appears to be a powerful option to find uncommon crystal forms. The crystallization of PBL was identified to be pressure controlled, thus the physical stability of PBL glass is higher than that of typical compounds.

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