Simulated migrating motor complex and its impact on the release properties of hydrophilic matrix systems

Abstract

Following ingestion, the dosage forms are exposed to high mechanical stresses, mainly due to the movement of gastric musculature and passage through the sphincters. The generated mechanical forces can have a profound impact on the release properties of the mechanically sensitive formulations, which may result in greater in vivo variability. The aim of the study was to prepare a new programme sequence for our bio-relevant in vitro dissolution model, the advanced gastric simulator (AGS), which would closely resemble the four phases of the migrating motor complex (MMC) and to evaluate the influence of the simulated mechanical stress on the drug release rate and the gel layer properties of the model hydrophilic matrix system. For this purpose, two kinds of HPMC matrix tablets were used, which have previously been tested in vivo. In vivo pressure measurements in human fasted stomach were gathered from literature and compared to the measurements obtained with the wireless motility capsule (WMC) in AGS. Dissolution studies conducted in AGS were compared to the experiments performed in USP2. Properties of the gel layer were evaluated with texture analysis and matrix erosion determination. Our in vitro measured pressure profiles of simulated MMC were found to be within the same range as those observed in vivo. The simulated MMC was shown to significantly affect the drug release kinetics from tested hydrophilic matrices. Compared to USP2, the AGS was shown to have a higher discriminatory power in distinguishing the differences in behaviour of the tested formulations, in accordance with in vivo data.