Solubility of cetilistat in neat solvents and preferential solvation in (acetone, isopropanol or acetonitrile) + water co-solvent mixtures

Abstract

The solubility of cetilistat in neat solvents of acetone, isopropanol, acetonitrile and water were determined experimentally by using the isothermal dissolution equilibrium method within the temperature range from (278.15 to 323.15) K under atmospheric pressure of 101.1kPa. At the fixed temperature, the mole fraction solubility of cetilistat was greater in acetone than in the other three neat solvents. They ranked as acetone>isopropanol>acetonitrile>water. The obtained solubilities were correlated with Apelblat equation. The largest value of relative average deviation was 0.86×10−2, and of root-mean-square deviation, 15.55×10−4. Furthermore, the preferential solvation parameters (δx1,3) of cetilistat in co-solvent mixtures of acetone (1)+water (2), isopropanol (1)+water (2) and acetonitrile (1)+water (2) were derived from their thermodynamic properties by means of the inverse Kirkwood–Buff integrals method. The values of δx1,3 varied non-linearly with the co-solvent (1) proportion in all the aqueous mixtures. The preferential solvation parameter was negative in water-rich mixtures but positive in intermediate composition and co-solvent-rich mixtures. In the latter case, it was conjecturable that cetilistat was acting as a Lewis acid with co-solvent molecules. The co-solvent action might be related to the breaking of the ordered structure of water around the polar moieties of cetilistat which increased the solvation of this drug. The solubility data and thermodynamic study expanded the physicochemical information about cetilistat in binary solvent mixtures, which was required in the pharmaceutical and chemical industries to save time and money in the optimization of the solubilization and/or crystallization process designs.