In order to investigate the influence of tri-sodium citrate, Na 3 Cit, and tri-potassium citrate, K 3 Cit, on the interaction of diphenhydramine-hydrochloride, DPH-HCl, and water, the volumetric, transport, and vapor liquid equilibria, VLE, properties were considered in this work. Thereby, density, speed of sound, and viscosity values for DPH-HCl drug in solutions containing Na 3 Cit, K 3 Cit, and H 2 O were measured in salt molality ranges of 0.05, 0.1, and 0.15 mol kg −1 and at T = 293.15, 298.15, and 303.15 K. Water activity and partial pressure of water data for systems of DPH-HCl + Na 3 Cit + H 2 O and DPH-HCl + K 3 Cit + H 2 O were also measured at 298.15 K. From these quantities, apparent molar volume, limiting apparent molar volume, apparent molar isentropic compression, limiting apparent molar isentropic compression, transfer standard volumes for DPH-HCl drug, and viscosity B-coefficients were calculated using the equations of Redlich−Meyer and Jones−Dole. The activities of water in these systems were correlated with the TNRF-mNRTL local composition based model.