Influence of Postprandial Intragastric Pressures on Drug Release from Gastroretentive Dosage Forms.

Despite extensive research in the field of gastroretentive dosage forms, this "holy grail" of oral drug delivery yet remained an unmet goal. Especially under fasting conditions, the reproducible retention of dosage forms in the stomach seems to be an impossible task. This is why such systems are often advised to be taken together with food. But also the postprandial motility can contribute significantly to the failure of gastroretentive dosage forms. To investigate the influence of postprandial pressure conditions on drug release from such systems, we used a novel in vitro dissolution tool, the dissolution stress test device. With the aid of this device, we simulated three different intragastric pressure profiles that may occur after postprandial intake. These transit scenarios were based on recently obtained, postprandial SmartPill® data. The tested systems, Glumetza® 1000 and Madopar® HBS 125, are marketed dosage forms that are based on different approaches to achieve proper gastric retention. All three transit scenarios revealed a highly pressure-sensitive drug release behavior, for both drugs. For Madopar® HBS 125, nearly complete drug release was observed even after early occurring pressures. Glumetza® 1000 seemed to be more resistant to these, most likely due to incomplete wetting of the system. On the contrary to these findings, data from standard dissolution tests using the paddle apparatus displayed controlled drug release for both systems for about 6 h. Based on these results, it can be doubted that established gastroretentive systems stay intact over a longer period of time, even under postprandial conditions.

In vitro simulation of realistic gastric pressure profiles.

Novel in vitro dissolution tools can aid the development of orally administered drugs by explaining dosage form related in vivo phenomena that are not explainable with standard test apparatuses. Such novel tools are able to mimic various parameters in accordance with gastrointestinal conditions. Hereby, in vivo occurring pressure events were shown to be of major importance since they largely affect dosage form disintegration, drug dissolution and subsequently resulting drug plasma concentration profiles. The aim of the present study was to investigate the feasibility of producing biorelevant pressure events with standard test apparatuses and with the dynamic open flow through test apparatus. For this purpose, we used the SmartPill®, a swallowable capsule that houses a pressure sensor and that was already applied to gather human in vivo data. Among the standard apparatuses, highest pressures were measured in the reciprocating cylinder apparatus and the disintegration tester. No relevant pressure peaks could be detected in the paddle apparatus and the mini paddle apparatus. In contrast, the dynamic open flow through test apparatus enabled the simulation of complete gastric pressure profiles as they occur in vivo. The present work underlines the potential of novel in vitro dissolution models as useful tools during the drug development process as well as for explanatory purposes.