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 (R) data. The tested systems, Glumetza (R) 1000 and Madopar (R) 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 (R) HBS 125, nearly complete drug release was observed even after early occurring pressures. Glumetza (R) 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 6h. Based on these results, it can be doubted that established gastroretentive systems stay intact over a longer period of time, even under postprandial conditions.