Spherical agglomerates of water-insoluble drugs

Spherical pellets of poorly soluble drugs (micronized griseofulvin, ibuprofen, indomethacin, sulfadiazine, or tolbutamide) were prepared by dispersing each drug in solutions of the ionic polysaccharides chitosan or sodium alginate, and then dropping these dispersions into solutions of the respective counterions tripolyphosphate or calcium chloride (CaCl2). The droplets instantaneously formed gelled spheres by inotropic gelation. Strong spherical beads with a narrow particle size distribution and low friability could be prepared with high yield and a drug content approaching 98%. The flow properties of micronized or needle-like drug crystals were significantly improved by this agglomeration technique when compared with nonagglomerated drug crystals. The ionic character of the polymers resulted in pH-dependent disintegration of the beads. Chitosan beads disintegrated in 0.1M HCl, while calcium alginate beads stayed intact in 0.1M HCl but rapidly disintegrated in simulated intestinal fluids. In addition to scanning electron microscopy, dissolution and disintegration tests were used to characterize the drug pellets.