Thermodynamic and Structural Characterization of a Mechanochemically Synthesized Pyrazinamide–Acetylsalicylic–Acid Eutectic Mixture

<b>Background/Objectives:</b> This study aims to develop a sustainable and environmentally friendly drug delivery system by synthesizing a novel drug-drug eutectic mixture (DDEM) of acetylsalicylic acid (ASA) and pyrazinamide (PZA) using a green and efficient mechanochemical approach. <b>Methods:</b> The DDEM was characterized using various techniques, including differential scanning calorimetry (DSC), thermogravimetry and differential thermal analysis (TG-DTA), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), and Raman spectroscopy. Binary phase diagrams and Tammann's triangle analysis determined the eutectic point. Density functional theory (DFT) calculations were performed on the starting compounds. The new system was evaluated for aqueous solubility, dissolution, and hygroscopicity. <b>Results:</b> A V-shaped binary phase diagram indicated the formation of a DDEM with a 2:1 molar ratio of ASA to PZA. A positive mixing enthalpy suggested a quasi-eutectic structure. The solubility of ASA and PZA increased by 61.5% and 85.8%, respectively, in the DDEM compared to the pure drugs. <b>Conclusions:</b> These findings highlight the potential of DDEMs to enhance drug properties and delivery. The synergistic interaction between ASA and PZA in the eutectic mixture may further improve therapeutic efficacy, warranting further investigation.