Mechanistic study of model drug release from HPMC matrices in fed gastric media

Abstract

Modified release (MR) formulations can persist in the gastrointestinal tract (GIT) for longer periods, being exposed to many variable conditions. After food intake, the gastric motility elevates and prolonged stress on the stomach content is expected. In this study, combination of food and mechanical stress effect on the model drug (paracetamol) release from HPMC matrix tablets was studied. Dissolution tests under simulated fed conditions were performed in the paddle apparatus (USP2) and reciprocating cylinder (USP3) and compared to the biorelevant dissolution model – the advanced gastric simulator (AGS). The absence of the mechanical stress in the conventional dissolution apparatuses caused apparently higher influence of the fed media (with high fat and protein content) on dissolution rate, possibly due to the deposition of poorly soluble fed media components onto the tablet surface – a process, which is unlikely to happen in vivo. Moreover, our results also indicate that the static apparatuses may have only a poor ability to identify the less robust formulations in the presence of osmotically active ingredients in the fed media. The present study therefore demonstrates that the use of mechanically bio-relevant dissolution apparatus, like the AGS, can provide an important additional insight into the interactions between food components and HPMC matrix tablets in the stomach.