The study highlights the importance of mixed micelles in enhancing the binding and solubilization properties of partially water-soluble medications, using zwitterionic cocoamidopropyl betaine (CAPB) and anionic sodium tetradecyl sulfate surfactants. Surface tension and fluorescence spectroscopy evaluated the critical micelle concentration (CMC) of CAPB-STS mixed micelle. The thermodynamic parameters were assessed using Clint, Rubingh, and Motomura’s approach, which showed a synergistic interaction between the CAPB and STS. UV spectroscopy technique was used to evaluate the applicability of mixed micelle to enhance the solubility and binding constant (Kb) of antibiotic azithromycin dihydrate (AZI). Kb values of AZI were increased from 2.301 to 3.415 and molar solubilization ratio (MSR) values of AZI were increased from 0.228 to 0.801 by decreasing αCAPB from 0.9 to 0.1. The result indicated that zwitterionic CAPB was an electrostatic interaction consisting of both attractive (−CH2COO¯ group) and repulsive (−N+ group) interactions with AZI (−NH+ group), causing AZI molecules to reside in the Stern layer. While STS consisted of a negative −SO4¯ head group, it caused increased electrostatic interaction, and AZI penetrated the palisade layer of mixed micelles. At 7.00 mmolL-1 concentration of αCAPB 0.1, the solubility of AZI in water was increased to 2.77 mmol/L from 0.0032 mmol/L. Additionally, after 8 h, the controlled release of AZI in PBS at pH 7.4 was 95.58 % and decreased up to 30.77 % at αCAPB 0.1 mixed micelles. The observation of controlled AZI release from αCAPB 0.9 to 0.1 indicates that AZI molecules were strongly bound to mixed micelles by both hydrophobic and electrostatic interactions. In the end, a mixed micelle of CAPB-STS could serve as a useful drug-solubilizing agent in pharmaceutical applications.