SUSTAINED-RELEASE THEOPHYLLINE TABLETS BY DIRECT COMPRESSION PART-1 -FORMULATION AND IN-VITRO TESTING

In an effort to reduce production costs, a simple, direct compression sustained release formulation consisting, principally, of the drug (th eophylline) and ethylcellulose was investigated. Ethylcellulose compac ts well and also retards drug release. In addition, matrices of this p olymer display slow surface erosion which can be enhanced by the incor poration of a swelling agent. This property was utilized in an attempt to decrease the attenuation of the release rate that is observed with matrix tablets that follow the Higuchi pattern of drug release. The r elease rate decreases because the external layers of the tablet become depleted and water must penetrate the deeper layers of the tablet to reach the remaining drug, The theophylline to ethylcellulose ratio and the tablet hardness were found to influence the rate of drug release. It was possible to sustain the release of a therapeutic dose of theop hylline over a 12-h period. Mathematical modeling showed an equally go od fit between the data and (a) the Higuchi model, or (b) a model that took into account diffusion, relaxation of the polymer, and erosion. However, the shape of the release curve was altered slightly in those tablets that eroded to a greater extent and residuals analysis illustr ated a better fit with the latter model. The erosion mechanism can be used to lessen one of the major problems associated with hydrophobic a nd plastic matrix tablets, i.e. the continuous reduction in the termin al release rate with time. (C) 1998 Elsevier Science B.V. All rights r eserved.