Preferential solvation of methocarbamol in aqueous binary co-solvent mixtures at 298.15 K

The preferential solvation parameters of methocarbamol in dioxane+water, ethanol+water, methanol+water and propylene glycol+water mixtures are derived from their thermodynamic properties by using the inverse Kirkwood-Buff integrals (IKBI) method. This drug is sensitive to solvation effects, being the preferential solvation parameter x(1,3), negative in water-rich and co-solvent-rich mixtures, but positive in mixtures with similar proportions of solvents, except in methanol+water mixtures, where positive values are found in all the methanol-rich mixtures. It is conjecturable that the hydrophobic hydration around the non-polar groups in water-rich mixtures plays a relevant role. Otherwise, in mixtures of similar solvent compositions, the drug is mainly solvated by co-solvent, probably due to the basic behaviour of the co-solvents; whereas, in co-solvent-rich mixtures, the preferential solvation by water could be due to the acidic behaviour of water. Nevertheless, the specific solute-solvent interactions present in the different binary systems remain unclear.