Characteristics of drug-phospholipid coprecipitates. II: Bioavailability studies of griseofulvin in rats.

The bioavailabilities of griseofulvin and dimyristoylphosphatidylcholine (DMPC) coprecipitates prepared from chloroform have been determined in rats. The dissolution rate of griseofulvin in pH 2.0 HCl:KCl buffer under sink conditions increased nonlinearly with an increase in DMPC in the coprecipitates. The initial dissolution rate, the amount dissolved after 60 min, Cmax, and AUC were all approximately twofold greater for coprecipitates than for griseofulvin over the range of 19:1 to 1.5:1 griseofulvin:DMPC weight ratio. In contrast, physical mixtures of griseofulvin:DMPC yielded results which were not significantly different from those of griseofulvin alone. The correlation between in vitro and in vivo parameters was at least 0.95. Thus, the reduction in particle size and solubilization of griseofulvin which is observed in vitro are believed to also occur in vivo and provide improved bioavailabilities.