A Novel Method for Combination of Ionic Conductivity and pH-metry Methods for the Determination of the Aqueous Solubility of a New Diisopropylammonium Hydrogenmaleate Crystalline Molecule

Abstract

Dissociation constant, solubility, and thermodynamic data are very important physicochemical parameters for biological substances and their knowledge is of fundamental importance for the validation of drugs. In addition to their low cost and accessibility, Conductometric and pH-metric methods seem to be particularly suitable for the determination of these parameters given the often weak acidic or basic nature of drugs. These parameters were determined for a new synthesized diisopropylammonium hydrogenmaleate (iPr2NH2-MA) crystalline molecule. Conductometric and pH-metric methods were used for this characterization. The pH-metric method lead to pKa1 = 3.6, pKa2 = 6.7 and pKa3 = 7.5, while the conductometric method made it possible to determine two pKa values which are pKa1 = 3.5 and pKa3 = 7.8. The values of the thermodynamic parameters calculated for the enthalpy change (∆rH0) and the entropy change (∆S) of the iPr2NH2-MA acidic dissociation reaction are of the order of ∆H = 25. 36 ± 0.06 kJ.mol-1 and ∆S = 6.08 ± 0.18 kJ.mol-1.K-1. In addition, the Gibbs free energy change (ΔG) of the molecule decreased as a function of temperature. The solubility varied between 1 and 84 mg mL-1 for pH values comprised between 3.5 and 8.5 and reached its maximum Smax = 84 mg mL-1 at pH 5.6. The dissociation process was found to be is non-spontaneous, endothermic and entropically favorable. These results demonstrated on the one hand the reliability and effectiveness of the Conductometric and pH-metric methods for the characterization of molecules with acidic and/or basic sites, and on the other hand the excellent physical and chemical properties of diisopropylammonium hydrogenmaleate (iPr2NH2-MA) crystalline molecule.