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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