Purpose <p>This study investigates the thermodynamic behaviour and solubilization efficiency of micellar systems composed of Triton X-100, Triton X-165, and Brij C10, individually and in mixtures, using ketoprofen as a poorly water-soluble model drug (BCS class II). The aim was to clarify the relationship between micellar stability, molecular interactions, and drug solubilization.</p> Methods <p>Critical micelle concentrations (<i>cmc</i>) were determined by fluorescence spectroscopy with pyrene as a probe. Non-ideality of mixed micelles was analysed by Rubingh’s model, Regular Solution Theory, and the Margules function. Thermodynamic parameters (g^E, s^E, h^E) were derived, and ketoprofen solubilization was quantified by HPLC as molar solubilization ratio (MSR) and excess solubilization parameters.</p> Results <p>Brij C10 exhibited the lowest <i>cmc</i>, reflecting strong hydrophobic contributions. Binary systems containing Brij C10 with Triton X-100 or X-165 showed pronounced synergism, indicated by negative β and gᴱ values. Triton-only systems behaved nearly ideally. Brij C10 alone provided the highest MSR, while binary Triton–Brij mixtures displayed partial antagonism in ΔMSR despite favourable thermodynamic stabilization. The ternary system was thermodynamically stable but less effective for ketoprofen solubilization due to packing constraints.</p> Conclusions <p>Micellar stability and solubilization efficiency are not always correlated. Brij-rich micelles showed superior ketoprofen solubilization, whereas overly stabilized ternary systems limited drug loading. These findings highlight the need to balance stability and flexibility when designing micellar carriers for hydrophobic BCS class II drugs.</p> Graphical Abstract <p></p>