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 (theophylline) and ethylcellulose was investigated. Ethylcellulose compacts well and also retards drug release. In addition, matrices of this polymer display slow surface erosion which can be enhanced by the incorporation 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 release 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 theophylline over a 12-h period. Mathematical modeling showed an equally good 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 illustrated a better fit with the latter model. The erosion mechanism can be used to lessen one of the major problems associated with hydrophobic and plastic matrix tablets, i.e. the continuous reduction in the terminal release rate with time.