Controlled-Release Theophylline Tablet Formulations Containing Acrylic Resins, III. Influence of Filler Excipient.

Abstract

The selection of a filler excipient was demonstrated to have a dramatic effect on the release properties of theophylline from matrix tablets containg an acrylic resin polymer as the retardant substance. Theophylline tablets were formulated to contain 60 percent drug, 28 percent filler excipient, 10 percent Eudragit S100, 1.5 percent fumed silica and 0.5 percent magnesium stearate. Release rates were most rapid when microcrystalline cellulose was the filler excipient and the slowest when calcium sulfate was used as the diluent. Dissolution rates decreased in acidic medium as the level of Eudragit S100 increased from zero to fifteen percent. In pH 7.4 phosphate buffer, USP, the converse held true because of the high solubility of the resin at this pH value. There was no difference between dissolution rates at pH 1.1 and pH 4.0. Tablet porosity was influenced significantly by the filler excipient. Higher porosity usually resulted in greater theophylline dissolution rates. When sucrose was employed as the filler excipient, tablet porosity was inversely related to tablet hardness.