Characterization and dissolution of fenofibrate solid dispersion systems

Abstract

In this study, solid dispersion systems of the sparingly water soluble drug, fenofibrate, in PEG 6000 and PVP were prepared and characterized. The effect of particle size of solid dispersions on the dissolution rate was also examined in ethanolic media at two stirring rates. DSC studies showed that fenofibrate was able to dissolve in the melt of PEG 6000 but not in PVP. Also, no transformation of the crystalline form of fenofibrate during the preparation of solid dispersions in these two carriers was observed using various methods. Furthermore, there was no indication of complex formation between fenofibrate and PEG 6000 from equilibrium solubility experiments. An enhancing effect of increasing the proportion of PEG 6000 was achieved only for large particles when using a medium containing 60% ethanol with stirring at 100 rpm. However, in the same medium but with stirring at 50 rpm, the dissolution rate was reduced with the decreasing particle size. As expected, the decrease in drug solubility in the medium containing 40 or 50% of ethanol slowed down the dissolution rate of fenofibrate from the PEG 6000 solid dispersions, and the dissolution rate was also dependent on the particle size. The dissolution rate of fenofibrate from the physical mixture was slower than that from the solid dispersion, and decreased with increasing proportion of PEG 6000 incorporated and with decreasing particle size. No evidence of a storage effect was obtained.