Nowadays, imperative efforts have been made to advance the drug performance, which leads to the discovery of novel drug preparations and delivery systems. An understanding of the interactions between drug molecules and biological membranes at the molecular level is necessary for the best design of such procedures. The choice of acceptable and suitable manufacturing chemicals in the pharmaceutical areas is made possible by the thermodynamic investigation, which offers comprehensive information on interactions. The aim of this work is measure the density and speed of sound data for two antibiotics drugs cefazolin sodium (CFZ.Na), and ceftriaxone sodium (CFT.Na) in aqueous solutions of the amino acids (glycine, L-alanine, and Lleucine) at temperature ranges 293.15−308.15 K. By correlation of the experimental data, some valuable thermodynamic parameters, i.e., apparent molar volume ,V φ , and apparent molar isentropic compressibility, κ φ were calculated. The Redlich-Meyer equation was used for fitting of these parameters. In addition, apparent molar isobaric expansion, E φ 0 , and Hepler's constant, (∂ 2 V φ 0 /∂T 2 ) P , were computed from the temperature dependency of density data. The values of Hepler's constant are indicated by the structure-making tendency of the drugs. Also, the co-sphere overlap model was employed to interpret the relation between hydrophilic-hydrophilic and ion-hydrophilic interactions, between drugs and amino acids.