Solubility of amiodarone hydrochloride in aqueous co-solvent mixtures revisited: IBKI preferential solvation analysis

Abstract The preferential solvation parameters ( δx 1,3 ) of amiodarone hydrochloride (AMDH) in three binary solvent mixtures of ethanol (1) + water (2), N -methyl pyrrolidone (NMP) (1) + water (2) and propylene glycol (1) + water (2) were derived from their available solubility data by using the inverse Kirkwood–Buff integrals method. The values of δx 1,3 varied non-linearly with the co-solvent (1) proportion in all the aqueous mixtures. For the system of ethanol + water, the values of δx 1,3 were negative in water-rich mixtures and co-solvent-rich mixtures, but positive in intermediate compositions. However, for the propylene glycol (1) + water (2) mixtures with composition 0.167  x 1 x 1 δx 1,3 values were positive indicating that AMDH is preferentially solvated by co-solvent. The positive δx 1,3 values could be explained on the basis of the higher acidic behavior of AMDH molecules interacting with the hydrogen acceptor groups present in co-solvent.