THE STABILITY AND INVITRO RELEASE KINETICS OF A CLOFIBRIDE EMULSION

Soybean and MCT submicron emulsions of clofibride were prepared using an optimal combination of phosphatidylcholine to poloxamer (molar ratio of 1:1). Both emulsions exhibited a mean droplet size in the range of 100-150 nm, and displayed identical Newtonian rheological behavior. The results of the accelerated stability tests indicated that the soybean emulsion was more resistant to various mechanical and thermal stresses than the MCT emulsion. The soybean emulsion remained stable even after an 18 month examination while the MCT emulsion showed signs of phase separation after 13 months storage at 25-degrees-C, confirming the findings of the accelerated tests. It was noted that the mean droplet size was not markedly altered by pH variation from 1.0 to 7.4 following 60 min of contact with the emulsion. Furthermore, the droplets of both emulsions remained practically unchanged as a function of contact time in artificial gastric medium. Whereas in artificial intestinal medium an increase in droplet size was observed only with the MCT emulsion. The in vitro release of clofibride from the emulsions was examined using various kinetic approaches. The dialysis sac technique was shown to be inadequate for drug release mechanism identification. However, two recent methods, the bulk-equilibrium reverse dialysis sac technique and the centrifugal ultrafiltration procedure, yielded rapid in vitro release profiles of clofibride from the emulsion. 70-90% of the clofibride content was released from the emulsion within 15-30 min, revealing that the kinetic process was probably controlled by the oil-water partition rate of the emulsion under perfect sink conditions. It was deduced from the overall results that the soybean emulsion of clofibride was definitely suitable for oral administration, since the presence of surface active agents may alter the drug absorption profile resulting in bioavailability enhancement.