Concentration Profiles of Carvedilol: A Comparison Between In Vitro Transfer Model and Dissolution Testing

Abstract

The study aims to investigate the transfer behavior of the weakly basic BCS class II model drug carvedilol from the stomach to the small intestine and compare the concentration profiles of carvedilol that were determined during the in vitro transfer model and dissolution testing. An in vitro transfer model, previously introduced by Kostewicz et al., was used in this study. A donor phase of simulated gastric fluid was used to predissolve Dilatrend® tablet (25 mg carvedilol). Media that simulate and cover the physiological pH and buffer capacity ranges of the intestinal fluid were used as acceptor phases. pH measurements were reported to investigate the effect of addition of donor phase containing predissolved carvedilol on lowering the pH of the acceptor media. The f2 similarity factor was used to compare the concentration profiles of carvedilol determined during the in vitro transfer model. Carvedilol was completely dissolved in all tested acceptor phases, resulted in no precipitation. The buffering capacity of the acceptor phase plays an important role in determining its pH. A discrepancy was found between the concentrations of carvedilol in all tested acceptor phases obtained using the transfer model and those reported using dissolution apparatus II in corresponding media. Results showed that dissolution testing using apparatus II might not be sufficient to predict its transfer from the stomach into the small intestine and that the in vitro transfer model may be more effective at mimicking the conditions in the gastrointestinal tract.