Abstract:
Matrix (non disintegrating) granules of theophylline have been formed and their dissolution characteristics
investigated for sustained release application. The polymeric granulations were formed by massing the drug
powder with a concentrated (40%w/w) ethanolic solution of an acrylatemethacrylate copolymer (ERS100R
). Wax granulations were also formed by massing the drug powder with previously melted carnuba wax followed by screening and drying. The content of polymer or wax in the resulting granules was 16.7%w/w. Conventional granules of theophylline were formed by massing the drug powder with starch mucilage (20%w/v). Resulting granules were subjected to particle size analysis and in vitro dissolution tests. The granules were further compressed to tablets (weight 500±4.2mg each) at a constant load (30 arbitrary units on the load scale). The tablets were subjected to hardness, disintegration and dissolution tests. The dissolution kinetics were also considered. The mean granule size was 646.5±4.3µm (conventional), 821.4±4.8µm (polymeric granulations) and 892.7±5.4µm (wax granulations), the matrix granules were therefore larger than the conventional granules. Dissolution of the granules generally followed a first order rate kinetic. The rate constant (k1) for the conventional, polymeric and wax granulations were (h-1): 0.53, 0.31 and 0.27 respectively. Thus, the wax granulations appeared to be more effective than the polymeric granulations in retarding drug release from the granules but the difference was not statistically significant (p>0.05). The tensile strength of tablets derived from the conventional, polymeric and wax granulations were (MNm-2) 0.85, 1.68 and 1.96 respectively, indicating that the matrix granules (compared with the conventional granules) produced harder tablets at the same compression load. The corresponding first order dissolution rate constants were (h-1): 0.46, 0.28 and 0.21. Thus, tableting of the matrix granules produced a slight but significant decrease in dissolution rates, attributable to the disintegration of the tablets to more compact particles.
