Microcalorimetry as an Effective Tool for the Determination of Thermodynamic Characteristics of Fulvic–Drug Interactions

The presence of pharmaceuticals in the environment can result in potentially dangerous situations. In soils and sediments, pharmaceuticals can be partially immobilized by interactions with humic substances. Interactions, thus, can strongly affect their mobility and bioavailability. An investigation of the thermodynamic aspects of the interactions is largely missing. Thermodynamic parameters are usually calculated on the basis of sorption experiments. Our study is focused on the direct measurements of the heat effect of interactions between fulvic acids and chosen drugs. Well-characterized fulvic sample standards provided by the International Humic Substances Society were used. Ibuprofen, diclofenac, and sulphapyridine were chosen as drugs. Isothermal titration calorimetry provided a complete set of thermodynamic characteristics of underlying processes—interaction enthalpy, entropy, and Gibbs energy. All studied interactions were found to be exothermic with heat liberation between −496 and −9938 J/mol. The lowest enthalpies were obtained for sulphapyridine and the highest ones for ibuprofen (on average). Changes in Gibbs energy were very similar for all studied interactions (20–28 kJ/mol). The highest change in entropy was determined for ibuprofen (73 J/mol·K); values obtained for diclofenac and sulphapyridine were comparable (57 and 56 J/mol·K, respectively).