Micellization and solubilization of a model hydrophobic drug nimesulide in aqueous salt solutions of Tetronic T904.

The micellar and phase behavior of an ethylene oxide-propylene oxide branched octablock copolymer Tetronic T 904 (hereafter written as T904) in water and NaCl solutions was examined. The copolymer shows a cloud point (CP) ranging from 74-65°C in the concentration range of 1-10% and forms aggregates (micelles) with a hydrodynamic diameter around 10-12nm in the temperature range 30-40°C. Stable, bluish solutions containing aggregates of variable size (several hundred nm in some cases) were observed even at temperatures much less than the critical micellization temperature (CMT=30°C for a 2% solution in water). The CP and the CMT markedly decrease in the presence of NaCl due to the dehydration of the polyethylene oxide shell. The size of the micelles in water or salt solutions increases at temperatures close to the CP as inferred from viscosity measurments. A model drug compound (nimesulide, NIM) was solubilized in T904 micelles which showed a remarkable increase in solubilization at higher temperature; however, a decrease in solubilization was observed in salt solutions. The thermodynamic parameters for solubilization were obtained, and the location of NIM in the copolymer micelles was investigated by UV-Visible spectroscopy.