The dispersion/incorporation of Eudragit S100 powder as a filler in cellulose acetate butyrate (CAB-551-0.01) microsphere containing theophylline was investigated as a means of controlling drug release. Microspheres of CAB-551-0.01 of different polymer solution concentrations/viscosities were prepared (preparations Z(O), Z(A), Z(B) and Z(C)) and evaluated and compared to microspheres of a constant concentration of CAB-551-0.01 containing different amounts of Eudragit S100 powder as a filler (preparations X-A, X-B and X-C). The organic solvent acetonitrile used was capable of dissolving the matrix former CAB-551-0.01 only but not Eudragit S100 powder in the emulsion-solvent evaporation method. The CAB-551-0.01 concentration in Z(A), Z(B) and Z(C) was equal to the total polymer concentration (CAB-551-0.01 and Eudragit S100 powder) in X-A, X-B and X-C, respectively. Scanning electron microscopy (SEM) was used to identify microspheres shape and morphology. In vitro dissolution studies were carried out on the microspheres at 37 degrees C (+/- 0.5 degrees C) at two successive different pH media (1.2 +/- 0.2 for 2 h and 6.5 +/- 0.2 for 10 h). Z preparations exhibited low rates of drug release in the acidic and the slightly neutral media. On the other hand, X preparations showed an initial rapid release in the acidic medium followed by a decrease in the release rate at the early stage of dissolution in the slightly neutral pH which could be due to some relaxation and gelation of Eudragit S100 powder to form a gel network before it dissolves completely allowing the remained drug to be released.