[Prolongation of theophylline derivative release with cellulose acetate based tablets]

Sustained-release tablets were prepared with three theophylline compounds of increasing solubility: theophylline, dyphylline and proxyphylline. Cellulose acetate was used as the matrix polymer. Two formulation parameters were studied: incorporated theophylline dose and percentage of polymer constituting the matrix. Drug release was enhanced as these parameter values rose. A mixed mineral and plastic matrix was formed by the two insoluble excipients, i.e. cellulose acetate and dibasic calcium phosphate for direct compression. Drug release could be optimized either by 2(2) factorial analysis or by multiple linear regression. Drug solubility was found to have an especially important influence on the release and did not allow sustained-release tablets to be obtained when it was too great. In the case of dyphylline and proxyphylline, only the additional application of a barrier-coating over the surface of the matrix tablets enabled prevention of their premature erosion and the massive release of drugs.