Solubilization of flurbiprofen with non-ionic Tween20 surfactant micelles: A diffusion 1H NMR study

Abstract

The diffusional behaviour of solubilized flurbiprofen (a poorly water soluble anti-inflammatory drug) in the presence of non-ionic Tween20 micelles was studied in an acidic environment (pH 3) using 1H NMR. Two different concentrations of flurbiprofen were considered, each at temperatures ranging from 15 to 55 °C. The variability of the hydrodynamic micellar diameter, which was calculated from diffusion 1H NMR data, revealed a structural rearrangement of the Tween20 micelles, caused by the solubilization of flurbiprofen. It was found that the additional peaks (at about 0.1 ppm upfield to the original ones), which appeared upon clouding, corresponded to a slowly diffusing population of solubilized drug molecules, in slow exchange (on an NMR timescale) with the faster diffusing population. This phenomenon was only observed in saturated samples at a temperature of at least 45 °C. For saturated samples at 55 °C, it was found that the flurbiprofen existed in dissolved, solubilized, as well as precipitated form. Combined diffusion and peak integration data revealed that the solubilized fraction was linked to micellar flurbiprofen (rapidly diffusing), small aggregates (slowly diffusing) and larger aggregates that were no longer observable by 1H NMR.