Physicochemical aspects of drug release. VI. Drug dissolution rate from solid particulate dispersions and the importance of carrier and drug particle properties

Abstract

Solid dispersions of a hydrophobic, sparingly soluble drug, griseofulvin, and a hydrophilic carrier, polyethylene glycol, were prepared by both a melting and a solvent method, with griseofulvin concentrations ranging from 1% to 20% w/w/ All the dispersions prepared contained particulate griseofulvin in which, the size, surface and shape characteristics of the particles had been determined. The aqueous solubilities of griseofulvin incorporated in solid dispersions were analyzed. The dissolution rate measurements were determined with the paddle method (100 rpm), of the USP XXI. It was concluded that the use of solid dispersion particles in the sieve size range 300–500 μm was preferable in dissolution testing, since problems due to both floatation and sedimentation could be avoided. For both the melting and the solvent methods used the dissolution rate decreased with increasing drug concentration. This effect was more pronounced in the solvent method where the reduction was almost entirely due to an increase in drug particle size. All the griseofulvin concentrations prepared by the melting method gave relatively fine particulate dispersions, and the drug particle size could only to a limited extent explain the dissolution rate data. It was found that the dispersions prepared by the melting method containing higher drug concentrations, corresponded to a reduction in the dissolution rate of the carrier. The aqueous solubility of griseofulvin was higher after incorporation in solid dispersion compared to the untreated raw material. The highest solubility was obtained for the melting method containing higher concentrations of griseofulvin.