title: Theophylline granule formulation prepared by the wet granulation method: comparison of in vitro dissolution profiles and estimation of in vivo plasma concentrations.
abstract: 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.
authors.affiliation: Department of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, University of Ege, Bornova, Izmir, Turkey. ercument.karasulu@ege.edu.tr
authors.forename: E
authors.initials: E
authors.lastname: Karasulu
authors.forename: S
authors.initials: S
authors.lastname: Apaydin
authors.forename: I
authors.initials: I
authors.lastname: Ince
authors.forename: I
authors.initials: I
authors.lastname: Tuglular
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D005079:Excipients / Q000737:chemistry; D005233:Fatty Alcohols / Q000737:chemistry; D016014:Linear Models; D008297:Male; D008956:Models, Chemical; D010316:Particle Size; D011208:Powders; D011237:Predictive Value of Tests; D011817:Rabbits; D012995:Solubility; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods; D013806:Theophylline / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency
chemical_list: D003692:Delayed-Action Preparations; D005079:Excipients; D005233:Fatty Alcohols; D011208:Powders; D013607:Tablets; C009316:stearyl alcohol; C013517:ethyl cellulose; D002482:Cellulose; D013806:Theophylline