Physicochemical investigation of phenobarbital sodium interactions with anionic bile salt micelles: Binding, partitioning, and micellization behavior

Understanding drug-surfactant interactions is crucial for optimizing pharmaceutical formulations. This study aimed to comprehensively investigate the physicochemical interactions between phenobarbital sodium (PS) and two anionic bile salts, sodium cholate (NaC) and sodium deoxycholate (NaDC), in aqueous media. UV-Vis spectroscopy, conductivity, surface tension, and viscosity measurements were employed to determine critical micelle concentration (CMC), binding constants (K b ), partition coefficients (K x ), interfacial parameters, and thermodynamic functions. Key results show PS significantly reduced the CMC of both bile salts (NaC: 1.30 ×10⁻⁴ M; NaDC: 1.92 ×10⁻⁵ M). NaDC consistently demonstrated superior surface activity (e.g., Γ max = 1.958 µmol·m⁻², pC 20 = 4.81) and more favorable thermodynamics for micellization (ΔG° m = −64.79 kJ/mol) and adsorption (ΔG° ads = −78.17 kJ/mol) compared to NaC. Furthermore, NaDC exhibited significantly stronger PS binding (K b ≈ 1.44 ×10⁶ M⁻¹) and partitioning (K x ≈ 2.85 ×10⁶), encapsulating ∼14 times more PS molecules per micelle than NaC. In conclusion, NaDC's enhanced hydrophobicity leads to superior micellization, drug binding, and solubilization capabilities, highlighting its considerable potential as an effective biosurfactant carrier for phenobarbital in pharmaceutical applications, offering valuable insights for drug delivery design.