Mt. Sheu et al., CHARACTERIZATION AND DISSOLUTION OF FENOFIBRATE SOLID DISPERSION-SYSTEMS, International journal of pharmaceutics, 103(2), 1994, pp. 137-146
In this study, solid dispersion systems of the sparingly water soluble
drug, fenofibrate, in PEG 6000 and PVP were prepared and characterize
d. 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 PE
G 6000 but not in PVP. Also, no transformation of the crystalline form
of fenofibrate during the preparation of solid dispersions in these t
wo carriers was observed using various methods. Furthermore, there was
no indication of complex formation between fenofibrate and PEG 6000 f
rom equilibrium solubility experiments. An enhancing effect of increas
ing the proportion of PEG 6000 was achieved only for large particles w
hen using a medium containing 60% ethanol with stirring at 100 rpm. Ho
wever, 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 etha
nol 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 m
ixture was slower than that from the solid dispersion, and decreased w
ith increasing proportion of PEG 6000 incorporated and with decreasing
particle size. No evidence of a storage effect was obtained.