Measurements of Binary Solid–Liquid Equilibrium of Anticancer Drug p-Toluenesulfonamide with Benzamide, Isonicotinamide, or Salicylamide

Abstract

Understanding the solid–liquid equilibrium (SLE) of active pharmaceutical ingredients (APIs) with excipients or other synergistic APIs is crucial for drug design and development. In this study, a poorly water-soluble anticancer API, p-toluenesulfonamide, was chosen as the model compound. SLE data and the eutectic conditions for three binary mixtures, p-toluenesulfonamide (1) + benzamide (2) (T_E = 354.2 K, x_1E = 0.453); p-toluenesulfonamide (1) + isonicotinamide (2) (T_E = 368.4 K, x_1E = 0.510); p-toluenesulfonamide (1) + salicylamide (2) (T_E = 371.7 K, x_1E = 0.538), were measured and reported using the differential scanning calorimetry (DSC) method. Simple eutectic behaviors were observed in these systems, with the eutectic and liquidus temperatures presented for each binary mixture at various compositions. The experimental eutectic composition was identified based on Tammann plots using the enthalpy values obtained from DSC measurements. Subsequently, the experimental liquidus temperatures were correlated using the Wilson and nonrandom two-liquid (NRTL) activity coefficient models, yielding the average absolute deviation in temperature (AADT) of less than 0.6%. These new SLE data provide valuable information for designing and developing drug formulations of p-toluenesulfonamide, thereby exploring potential applications.