The Expanded Hansen Approach to Solubility Parameters. Paracetamol and Citric Acid in Individual Solvents

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Abstract
In this study two solubility‐parameter models have been compared using as dependent variables the logarithm of the mole fraction solubility, lnX2e, and ln(α)/U (originally used in the extended Hansen method), where α is the activity coefficient and U is a function of the molar volume of the solute and the volume fraction of the solvent. The results show for the first time the proton‐donor and ‐acceptor hydrogen‐bonding capacities of paracetamol, as measured by the acidic and basic partial‐solubility parameters. The influence of solvents on the differential scanning calorimetry (DSC) pattern of the solid phases was also studied in relation to the solubility models tested. Citric acid was chosen as a test substance because of its high acidity and its proton donor capacity to form hydrogen bonds with basic solvents. The partial acidic and basic solubility parameters obtained from multiple regression were consistent with this property, validating the model chosen. The results show that the more direct lnX2e variable was more suitable for fitting both models, and the four‐parameter model seemed better for describing the interactions between solvent and solute.

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