Abstract
This research work reports the cilostazol (form A) dissolution in (ethylene glycol / ethanol + water) mixtures. The co-solvency phenomenon only occurs in mixture of ethanol + water, the maximum solubility in mole fraction is 3.034 × 10-3 at the composition of 0.85. It was found that the solvation performance of cilostazol in two mixtures mainly depend on the ability of forming hydrogen bond (H-bond) of the solutions and van der Waals interaction. According to the preferential solvation results, it is conjecturable that cilostazol molecules are preferentially solvated by water in water-rich regions. With the increase of alcohol concentration, the destruction of water molecular ordered structure by alcohol through hydrogen bond, and solute molecules are preferentially solvated by ethanol and EG. Nonetheless, when 0.86 < x1 < 1 in mixture of ethanol + water, solute molecules are preferentially solvated by water again. The calculation of radial distribution function (RDF) between the atoms of H and O for ethanol and the atoms of N and H for solute is to achieve the interaction of the solute and solvents. The correlation fitting was performed for the solubility data through Jouyban Acree model and its derivative models, and the statistical analysis showed that the Apelblat-Jouyban Acree model is more suitable to present the solubility correlation. Meanwhile, the values of apparent molar standard dissolution enthalpy (ΔHsolo) and apparent molar standard dissolution entropy (ΔSsolo) are positive in each solvents, which reveals that the dissolution process of cilostazol form A is endothermic and entropy favorable within the given temperature range.
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