Abstract <p>Density, ultrasonic velocity and refractive index of antibacterial pyridoxine hydrochloride (<i>m</i> = 0.02, 0.04, 0.06, 0.08, 0.10, and 0.12 mol kg^–1) and neomycin sulphate (<i>m</i> = 0.005, 0.02, 0.04, 0.06, 0.08, and 0.10 mol kg^–1) drugs in aqueous-urea solutions were measured at different temperatures (<i>T</i> = 303.15, 308.15, and 313.15 K). The measured properties were used to calculate derived thermoacoustical properties such as isentropic compressibility, acoustic impedance, intermolecular free length and relative association of different systems. The effect of temperature and co-solute urea concentrations on acoustical properties of studied drugs has been evaluated and interpreted in terms of molecular interactions and structural fittings in drug solutions. The studies have implications in the solubility and bioavailability of studied antibacterial drugs.</p>