Comparison of polyethylene glycol and polyoxyethylene stearate as excipients for solid dispersion systems of griseofulvin and tolbutamide II: dissolution and solubility studies.
The effects of joining a long-chain ester group with the polyethylene glycol molecule were studied in solid dispersion systems by comparing the dissolution and solution properties of such systems prepared from polyethylene glycol 2000 with those prepared from the nontoxic, water-soluble, solid excipient polyoxyethylene 40 stearate. Solid dispersion systems of griseofulvin and tolbutamide were prepared by physical mixing, fusion, or coprecipitation from ethanol. The compacted dispersion systems dissolved by progressive erosion, releasing floccules of microcrystals. The released microcrystals of tolbutamide (3--10 micrometer) were smaller than the original drug particles (approximately 20 micrometer), but those of griseofulvin were of similar size to the original particles. In general, the rate of and extent of release of each drug were greater from polyoxyethylene 40 stearate than from polyethylene glycol 2000 dispersions. The aqueous solubility and dissolution rate of nondisintegrating disks of each pure drug increased only slightly in the presence of polyethylene glycol 2000 but increased considerably with increasing concentration of polyoxyethylene 40 stearate due to micellar solubilization. Thus, polyoxyethylene 40 stearate generally is superior to polyethylene glycol 2000 in promoting the dispersion of the drugs in solids, disintegration of the compacted solids, and solubilization of the drug during dissolution.
D011232:Chemical Precipitation; D005079:Excipients; D006118:Griseofulvin; D010316:Particle Size; D011092:Polyethylene Glycols; D012995:Solubility; D013500:Surface Tension; D014044:Tolbutamide; D014783:Viscosity
D005079:Excipients; D006118:Griseofulvin; D011092:Polyethylene Glycols; D014044:Tolbutamide