Simulating in vivo conditions using in vitro methods allows for a fairly good approximation of physiological conditions. One of the in vitro biorelevant devices is the advanced gastric simulator, which was developed at Lek d.d. in Ljubljana in cooperation with the Faculty of Mechanical Engineering, University of Ljubljana. Advanced gastric simulator imitates in vivo conditions due to anatomical similarities to human stomach, ability to mimic gastric wall contraction, flexible silicone container and migrating motor complex simulation, which occurs in fasting conditions. In this way, it significantly differentiates in performance with respect to the paddle dissolution apparatus. The aim of this master's thesis was to evaluate the mechanical impact of the advanced gastric simulator on hydrophilic matrix tablets and to investigate the effect of stomach transit on the tablet and how it affects the release kinetics. We also investigated the impact of the biorelevant fasted state simulated gastric fluid compared to 0,01M HCl with ions in both devices.
Firstly, we were using texture analyser to measure gel thickness of two tablet formulations with different composition. We measured a reduction in gel layer thickness after swelling in the advanced gastric simulator compared to the paddle dissolution apparatus. Advanced gastric simulator passes strong mechanical and hydrodynamic forces directly onto the surface of the swelled samples, thus removing the surface layers of the matrix more effectively. The erosion of gel layer is also more pronounced compared to the paddle dissolution apparatus. The choice of the biorelevant medium does not have a significant impact on the gel thickness and erosion. Moreover, we investigated the influence of the advanced gastric simulator and intestine model for simulating peristaltic action on the release of dipyridamole from a new formulation. The in vivo pressure conditions in the lumen of the stomach and the small intestine were imitated relatively good by both devices. Consequently, dipyridamole release kinetics was faster and the total release was greater than in the paddle dissolution apparatus. Furthermore, the pH gradient was determined within the gel layer of the formulation in both devices using a complex cryostatic method. Our results showed significant differences in the release processes of tested pharmaceutical forms in classical and biorelevant apparatuses. These differences were also explained by the use of advanced analytical technologies, such as the surface pH measurements and texture analysis.
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