From Solution Studies of Pharmaceuticals (Aspirin and Related Compounds) to the Thermodynamics of Aspirin-β-Cyclodextrin Interaction in water and N,N-Dimethylformamide

The solution behavior of pharmaceuticals (acetylsalicylic acid, 4-acetoxybenzoic acid and 5-acetylsalicylic acid) in water and N,N-Dimethylformamide (DMF) at 298.15 K were investigated through solubility, conductance and calorimetric measurements. Taking into account the formation of ion pairs of these pharmaceuticals in water, the solution Gibbs energies of the dissociated electrolytes in this solvent were calculated. Thus, the solution thermodynamics of these compounds in water are reported using enthalpy data obtained by calorimetry. These pharmaceuticals undergo solvation when exposed to a saturated atmosphere of DMF. As the composition of the solid is not the same as that in solution, the Gibbs energy of the solutions of these compounds could not be obtained; only enthalpy data are reported. The thermodynamics of the interaction of acetylsalicylic acid (aspirin) with β-cyclodextrin in water and DMF is fully discussed, emphasizing the two different processes that take place in water at the two different pHs. In all cases, the favorable Gibbs energies for these processes are entropically controlled, mainly resulting from the higher dehydration/desolvation that the receptor undergoes upon interaction with the guest.