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

•Preferential solvation of AMDH in three co-solvent mixtures was discussed.•Preferential solvation parameters were derived by IKBI method.•AMDH was preferentially solvated by co-solvent in intermediate composition.•Preferential solvation in ethanol system is different from that in the other systems.

The preferential solvation parameters (δx1,3) 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 δx1,3 varied non-linearly with the co-solvent (1) proportion in all the aqueous mixtures. For the system of ethanol + water, the values of δx1,3 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 < x1 < 1 and NMP (1) + water (2) mixtures with composition 0.20 < x1 < 1, the δx1,3 values were positive indicating that AMDH is preferentially solvated by co-solvent. The positive δx1,3 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.

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