Theophylline granule formulation prepared by the wet granulation method: comparison of in vitro dissolution profiles and estimation of in vivo plasma concentrations.

The primary and secondary objectives of this study were to develop and evaluate the predictability of in vitro-in vivo correlation models for theophylline sustained release (SR) granules. Theophylline SR granules meeting the USP Drug Release Test criteria were prepared using ethyl cellulose (EC) and/or stearyl alcohol (SA) and the wet granulation method. In vitro dissolution studies of granule formulation were performed, and a commercial dosage form was prepared using USP XXIII apparatus II at pH 4.5. Differences and similarities between in vitro dissolution curves were compared using both model-dependent (t-test) and -independent (f1, f2 test) statistical techniques, and it was shown that the three dissolution profiles i.e model-dependent, model-independent, and methods based on ANOVA were very similar. The in vivo performance of the commercial dosage form was tested by oral route using male rabbits and in vitro-in vivo correlations were established. This study indicates that the dosage forms with similar in vitro dissolution profiles may have a similar in vivo performance, and that this performance could be estimated using appropriate correlation equations.