Solubility and Thermodynamic Properties of Sulfamethazine–Saccharin Cocrystal in Pure and Binary (Acetonitrile + 2-Propanol) Solvents

Abstract

In this work, a new crystallization method was used to prepare two polymorphs of sulfamethazine–saccharin (SMT–SAC) cocrystal in bulk. The purity and crystal form of both polymorphs were confirmed by optical microscopy, scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. Moreover, the solubility of the stable form (form II) was determined by gravimetric analysis in nine pure solvents and one binary (acetonitrile + 2-propanol) solvent at temperatures ranging from 278.15 to 348.15 K at atmospheric pressure. Experimental data were correlated using the modified Apelblat model, the λh equation, the nonrandom two-liquid (NRTL) model, the Jouyban–Acree model, and the CNIBS/Redlich–Kister model. Finally, the apparent thermodynamic properties, such as $$\Delta_{\text{dis}} G$$, ΔdisH, and ΔdisS, were calculated on the basis of the activity coefficient obtained by the NRTL model. All the models correlate well, and all the experimental and calculated results indicate that the dissolution behavior of SMT–SAC cocrystal form II is a spontaneous, endothermic, and entropy-driven process.