Physical characteristics of freeze-dried griseofulvin-lipids nanoparticles.

We have attempted to prepare micronized drug particles and to maintain the micronized state long-term in order to improve the solubility of a practically insoluble drug, griseofulvin (GF). GF nanoparticles (GFNPs) prepared by high-pressure homogenization were micronized to about 45 nm (mean particle size). GFNPs were subjected to transmission electron microscopy (TEM) observation. The mean particle size remained at about 50 nm for 3 months at 25 degrees C. However, increased to about 300 nm in 6 months. After 5% (w/v) sugar was added, GFNP was freeze-dried and rehydrated. The mean particle size of the rehydrated GFNPs was about 160 nm when the sugar was a monosaccharide. In contrast, it was about 55-65 nm when the sugar was a disaccharide. The powder X-ray diffraction pattern of the monosaccharide-containing freeze-dried GFNPs revealed a crystal state of sugar. On the other hand, that of the disaccharide-containing freeze-dried GFNPs indicated an amorphous state of sugar. From this result, it is considered that the high viscosity of an amorphous sugar prevents GFNPs from aggregating through retardation of molecular movement. Freeze-dried GFNPs stored for six months at 25 degrees C showed a good re-dispersibility. After the rehydration the mean particle size of GFNPs was 55-65 nm. It was found that freeze-dried GFNPs containing sucrose, maltose or trehalose were stable for longer periods than GFNP suspensions.