Characteristics of drug-phospholipid coprecipitates I: Physical properties and dissolution behavior of griseofulvin-dimyristoylphosphatidylcholine systems.

Solid dispersions of griseofulvin and dimyristoylphosphatidylcholine (lecithin) have been prepared as both coprecipitates and physical mixtures, and their physical characteristics and dissolution behavior compared with pure griseofulvin. The dissolution of the physical mixtures was similar to pure drug, but the coprecipitates yielded a 3.5-fold greater initial dissolution rate and a limiting concentration after 60 min which was 72% greater at a griseofulvin-lecithin weight ratio of 19:1. Increasing the lecithin content to 1.5:1 compositions resulted in only a further 50% increase in the initial dissolution rate and a further 12% increase in the limiting concentration. The effect of the pH of the medium on dissolution was slight, but varied with the composition of the system. The phase diagram indicated that these systems have no significant eutectic or solid solution formation. X-ray diffraction spectra further showed that freshly prepared or aged coprecipitates contained griseofulvin crystals, and photomicrographs showed that the crystals essentially retained their characteristic shapes and sizes in all systems. Differential thermal analysis yielded heats of fusion that gave a good linear correlation with the percent of griseofulvin dissolved from coprecipitates at all time intervals, but not with physical mixtures. Furthermore, aged coprecipitates underwent a slower rate of dissolution compared with fresh samples. The results are interpreted to suggest that griseofulvin undergoes improved dissolution from coprecipitates due to the formation of crystals of lower stability. In addition, the rapid dispersion of lecithin in the aqueous medium (as seen microscopically) entraps griseofulvin in myelinic structures and liposomes and effectively increases the saturation concentration of drug in the diffusion layer during the dissolution process.