THE EFFECT OF PARTICLE-SIZE AND SHAPE ON THE SURFACE SPECIFIC DISSOLUTION RATE OF MICROSIZED PRACTICALLY INSOLUBLE DRUGS

The effects of both particle shape and size on the dissolution rate of sparingly soluble micro-particles have been studied. Griseofulvin, three different qualities of barium sulphate, oxazepam and glibenclamide were chosen as the model substances. As these materials differed in both particle size (from 1.8 to 3.8 mu m) and particle shape (from rounded, isodiametric to flaky or irregular particles), different combinations of particle size and shape were used to investigate their combined effect on the dissolution rate. The surface specific dissolution rate was determined, using a Coulter counter technique. The ratio of this value to the equilibrium solubility was calculated for all materials and its relation to the shape and size of the micro-particles was investigated. The results obtained indicated that the dissolution rates of sparingly soluble drugs are related to the particle shape as well as to the particle size. For particles of the same size, the dissolution rate decreased as the level of flakiness and irregularity increased. This phenomenon can be explained by an increase in the average hydrodynamic boundary layer thickness as the particles become more irregular. Therefore, the product of the surface shape factor and mean particle diameter was used to discuss the combined effect of these factors on the dissolution rates of sparingly soluble drugs.