The physicochemical property of water-insoluble drug piroxicam (PY) in the presence of two. ionic-mixed micellar systems was investigated. The two systems were pluronic L-81-sodium dodecyl sulfate (SDS), a nonionic-anionic; and pluronic L-81-cetyl pyridinium bromide (CPB), a nonionic-cationic. The characterizations employed were UV–visible spectroscopy, FTIR spectroscopy, conductivity, cloud point and cyclic voltammetry measurements. The results from UV spectra showed that there was different behaviour of piroxicam with anionic and cationic mixed micelles. But, the common observation for both sets was that the drug absorption with a mixed micellar system displayed an intermediate position compared to both the single micellar systems. There was short and strong bond formation in the complex formed between piroxicam and mixed micelles as evidenced by FTIR studies. The conductivity measurements revealed that the drug and mixed micelle in the produced complex have a stable and spontaneous binding. The free energy of micellization ∆Gm was observed to be -18.04 kJ/mole for piroxicam [PY + L-81] + SDSa group and -37.73 kJ/mole for piroxicam [PY + L-81] + CPBc group. The higher negative value of the nonionic-cationic system indicates greater stability of the drug in the system. The cloud point measurements corroborated this finding. The cyclic voltammetry study of piroxicam with ionic surfactant SDS/CPB displays greater electrostatic interaction in mixed micelle combination (PY/CPB/L-81) compared to single micelle combination (PY/CPB) and pure drug. The combination is novel for the hydrophobic drug piroxicam which can be used by the formulation scientist. Interaction of drug (PY) and surfactant (SDS/CPB) presence of pluronic L-81 [ABSTRACT FROM AUTHOR]