INVESTIGATIONS ON THE MICELLIZATION BEHAVIOR OF FENOPROFEN SODIUM

The aim of the present study was to investigate the micellisation beha viour of the non-steroidal anti-inflammatory drug fenoprofen sodium in aqueous solutions. The methods used were foam stability measurements, H-1-NMR, solubilisation, photon correlation spectroscopy (PCS) and tr ansmission electron microscopy (TEM). Results from surface tension mea surements performed in a previous study were included. A great discrep ancy between critical values from different experimental methods was f ound. Methods that detect changes in the surface properties of aqueous fenoprofen sodium solutions suggest that the critical concentration w as 1.510(-2) mol/L, while methods that detect changes in the bulk pha se led to a critical concentration of 1.210(-1) mol/l. In the concent ration range between 1.510(-2) and about 1.0*10(-1) mol/l no formatio n of aggregates could be detected (concluded from the absence of an up field shift of the phenyl proton signals in the NMR measurements and t he finding that the oily, practically water insoluble fenoprofen acid could not be solubilised by fenoprofen sodium solutions below concentr ations of 1.010(-1) moll fenoprofen sodium). Association of fenoprofe n sodium molecules to micelles starts at concentrations between 1.0 an d 1.210(-1) mol/L. In conclusion, the determination of the critical m icelle concentration from surface tension measurements does not allow the determination of micellisation phenomena in the case of fenoprofen sodium. Further methods are required to assure micellisation. Photon correlation spectroscopy and TEM support the assumption that fenoprofe n sodium forms disclike micelles, although with both methods the micel le size could not exactly be determined. From differences in the chemi cal shift of the two phenyl rings of fenoprofen sodium it was conclude d that the micelles have a bilayer or partially overlapping bilayer st ructure. (C) 1997 Elsevier Science B.V.