Solubility and solution thermodynamics of sulfamerazine and sulfamethazine in some ethanol + water mixtures

• The solubility of sulfamerazine and sulfadiazine was maximal in a co-solvent mixture and minimal in pure water.
• Thermodynamic quantities of solution and mixing were obtained for sulfamerazine and sulfamethazine.
• Non-linear plots of ΔmixH° vs. ΔmixG° compensation were found for sulfamerazine and sulfamethazine at 303.0 K.

The solubility of sulfamerazine (SMR) and sulfamethazine (SMT) in some ethanol + water cosolvent mixtures was measured at five temperatures from 293.15 to 313.15 K in all the polarity range provided by the aqueous mixtures. The mole fraction solubility of both drugs was maximal in the mixture 0.80 in mass fraction of ethanol (δ = 30.0 MPa1/2) and minimum in pure water (δ = 47.8 MPa1/2) at all the temperatures studied. The thermodynamic functions Gibbs energy, enthalpy, and entropy of solution were obtained from these solubility data by using the van’t Hoff and Gibbs equations. Thermodynamic quantities of mixing were also calculated by using some calorimetric values related to the drugs fusion process reported in the literature. Non-linear enthalpy–entropy relationships were observed for both drugs in the plot of enthalpy vs. Gibbs energy of mixing. The plot of ΔmixH° vs. ΔmixG° shows three different trends according to the slopes obtained when the mixtures composition changes. Accordingly, the driving mechanism for SMR solution process in water-rich is the entropy; whereas, from 0.20 mass fraction of ethanol to neat ethanol the process is enthalpy-driven. For SMT the process is driving by entropy in water-rich and ethanol-rich mixtures but driven by enthalpy in mixtures from 0.30 to 0.80 mass fraction of ethanol. The behavior of SMT is similar to the ones exhibited by the similar drugs sulfapyridine and sulfadiazine in the same co-solvent mixtures.