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.
KEY WORDSSmartPill gastric pressure dissolution stress test device in vitro model gastroretentive dosage forms
This work has received financial support from the Innovative Medicines Initiative Joint Undertaking (http://www.imi.europa.eu) under Grant Agreement No. 115369, resources of which are composed of financial contribution from the European Union Seventh Framework Program and EFPIA companies in kind contribution, as well as from the Federal Ministry of Education and Research, Germany (FKZ 03IPT612X, InnoProfile-Transfer).
- 7.Goetze O, Treier R, Fox M, Steingoetter A, Fried M, Boesiger P, et al. The effect of gastric secretion on gastric physiology and emptying in the fasted and fed state assessed by magnetic resonance imaging. Neurogastroenterol Motil. 2009;21(7):725–e72. https://doi.org/10.1111/j.1365-2982.2009.01293.x.CrossRefPubMedGoogle Scholar
- 10.Cassilly D, Kantor S, Knight LC, Maurer AH, Fisher RS, Semler J, et al. Gastric emptying of a non-digestible solid: assessment with simultaneous SmartPill pH and pressure capsule, antroduodenal manometry, gastric emptying scintigraphy. Neurogastroenterol Motil. 2008;20(4):311–9. https://doi.org/10.1111/j.1365-2982.2007.01061.x.CrossRefPubMedGoogle Scholar
- 15.Garbacz G, Wedemeyer RS, Nagel S, Giessmann T, Mönnikes H, Wilson CG, et al. Irregular absorption profiles observed from diclofenac extended release tablets can be predicted using a dissolution test apparatus that mimics in vivo physical stresses. Eur J Pharm Biopharm. 2008;70(2):421–8. https://doi.org/10.1016/j.ejpb.2008.05.029.CrossRefPubMedGoogle Scholar
- 18.Garbacz G, Golke B, Wedemeyer RS, Axell M, Söderlind E, Abrahamsson B, et al. Comparison of dissolution profiles obtained from nifedipine extended release once a day products using different dissolution test apparatuses. Eur J Pharm Sci. 2009;38(2):147–55. https://doi.org/10.1016/j.ejps.2009.06.010.CrossRefPubMedGoogle Scholar
- 19.Schneider F, Grimm M, Koziolek M, Modeß C, Dokter A, Roustom T, et al. Resolving the physiological conditions in bioavailability and bioequivalence studies: comparison of fasted and fed state. Eur J Pharm Biopharm. 2016;108:214–9. https://doi.org/10.1016/j.ejpb.2016.09.009.CrossRefPubMedGoogle Scholar
- 34.Brun R, Michalek W, Surjanhata BC, Parkman HP, Semler JR, Kuo B. Comparative analysis of phase III migrating motor complexes in stomach and small bowel using wireless motility capsule and antroduodenal manometry. Neurogastroenterol Motil. 2012;24(4):332–e165. https://doi.org/10.1111/j.1365-2982.2011.01862.x.CrossRefPubMedGoogle Scholar