Abstract
Based on van't Hoff and Gibbs equations the thermodynamic functions free energy, enthalpy, and entropy of solution, mixing and solvation of acetaminophen in ethanol + water cosolvent mixtures, were evaluated from solubility data determined at several temperatures. The solubility was greater at 90% m/m of ethanol at all temperatures studied. This result shows clearly the cosolvent effect present in this system. The solvation of this drug in the mixtures increases as the ethanol proportion is also increased. By means of enthalpy-entropy compensation analysis, a more complex behavior for solution was found with respect to that exposed previously in literature. From 0% up to 10% m/m of ethanol and from 90% up to 100% of ethanol, entropy driving was found, while from 20% up to 60% of ethanol, enthalpy driving was found. These facts would be explained in terms of a losing of water-structure in addition to a diminishing in the energy required for cavity formation in the solvent for mixtures from 20% up to 60% of ethanol. Nevertheless in the ethanol-rich mixtures the intermolecular mechanisms involved in the solution process should be more complex including other physicochemical considerations.
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