Herein, we have accounted for the interaction between a non-steroidal anti-inflammatory drug ibuprofen (IBF) and non-ionic surfactant polyethoxyglycol t-octylphenyl ether (TX-100 (4-(1,1,3,3-tetramethylbutyl) phenyl-polyethylene glycol) and TX-114 ((1,1,3,3-tetramethylbutyl) phenyl-polyethylene glycol)), in aqueous urea solutions using tensiometric and fluorimetric techniques at T = 298.15 K. Surface tension measurements were carried out to evaluate the critical micelle concentrations (cmc) of the drug and surfactant as well as their mixtures of varying compositions. An increase in the surface charge of the micelles was observed with the addition of urea followed by halt of micelles formation. Various physicochemical parameters, such as, cmc values of the mixture, micellar mass fraction (X-1(Rub)) of surfactants (TX-100/TX-114), interaction parameters (beta) at the monolayer air-water interface and in bulk solutions, different thermodynamic parameters and activity coefficients (f(1)(m); f(2)(m)) for the non-ionic surfactant and drug in the mixed micelles, were determined by using the approach of Clint, of Rubingh, and of Rosen. All results identified synergism and attractive interactions in the mixed systems of (drug-surfactant) mixtures and showed effective involvement of the non-ionic surfactant (TX-100/TX-114) component in the mixture. Micelle aggregation numbers (N-agg), evaluated by using steady-state fluorescence quenching studies, suggest that the contribution of non-ionic surfactant was always more than that of the drug. Micropolarity (I-1/I-3), Stern-Volmer binding constants (K-sv) and the dielectric constant (D-exp) of mixed systems have also supported the synergistic behavior of the mixed amphiphilic systems. (C) 2014 Elsevier Ltd. All rights reserved.