Effect of particle size and film thickness on bioavailability and ulcerogenicity of encapsulated flufenamic acid

Abstract

Encapsulation of four batches of flufenamic acid (FFA) having mean particle diameters of 75, 130, 180 and 225 μm with cationic acrylic resin (Eudragit E) have been achieved using a fluidized-bed granulator (Glatt AG). The bioavailability and gastric ulcerogenic activity of the encapsulated and plain drug for each batch have been simultaneously assessed in rats subjected to physical restraint stress. Encapsulated batches of FFA showed significantly higher plasma levels and lower ulcerogenic activities than those of plain batches. Although encapsulated batches showed comparable plasma levels, compared with each other, they varied greatly as regards their ulcerogenic activities. The smaller the mean diameter of microcapsules of a batch the lower its ulcerogenic activity. A linear correlation was found between the film thickness of Eudragit in microcapsules and the ulcer indices of various encapsulated batches. Plain FFA batches, however, showed comparable plasma levels as well as comparable ulcer data, when compared with each other, within the size range studied.