Solubility modelling and preferential solvation of paclobutrazol in co-solvent mixtures of (ethanol, n-propanol and 1,4-dioxane) + water

Abstract

The equilibrium solubility of paclobutrazol in co-solvent mixtures of ethanol (1)+water (2), n-propanol (1)+water (2) and 1,4-dioxane (1)+water (2) were determined experimentally by using isothermal dissolution equilibrium method within the temperature range from (278.15 to 313.15)K under atmospheric pressure (101.1kPa). At the same temperature and mass fraction of co-solvent, the mole fraction solubility of paclobutrazol in the three binary co-solvent mixtures obeyed the following order from high to low: 1,4-dioxane (1)+water (2)>n-propanol (1)+water (2)>ethanol (1)+water (2). The preferential solvation parameters were derived from their thermodynamic solution properties by means of the inverse Kirkwood–Buff integrals. The preferential solvation parameters for ethanol, n-propanol or 1,4-dioxane (δx1,3) were negative in water-rich mixtures but positive in compositions from 0.24 (0.19, 0.18) in mole fraction of ethanol (n-propanol or 1,4-dioxane) to pure ethanol (n-propanol or 1,4-dioxane). The preferential solvation magnitude of paclobutrazol by the co-solvent was highest in ethanol (1)+water (2) mixtures and lowest in n-propanol (1)+water (2). It was conjecturable that in the former case hydrophobic hydration around the aromatic rings played the main role in the drug’s solvation. The higher solvation by ethanol (n-propanol or 1,4-dioxane) in intermediate compositions and in colsolvent-rich mixtures could be explained in terms of the higher basic behaviour of this co-solvent interacting with the Lewis acidic groups of the paclobutrazol. Besides, the drugs’ solubilities were mathematically represented by using the Jouyban-Acree model, van’t Hoff-Jouyban-Acree model and Apelblat-Jouyban-Acree model obtaining average relative deviations lower than 4.73% for correlative studies.