Impact of acid-reducing agents on gastrointestinal physiology and design of biorelevant dissolution tests to reflect these changes

Abstract Background Of the various drug therapies that influence gastrointestinal (GI) physiology, one of the most important are the acid reducing agents (ARAs). Since changes in GI physiology often influence the pharmacokinetics of drugs given orally, there is a need to identify in vitro methods with which such effects can be elucidated. Objective Literature concerning the effects of ARAs (antacids, H 2 -receptor antagonists and proton pump inhibitors) on GI physiology are reviewed with the aim of identifying conditions under which drugs are released after oral administration in the fasted state. In vitro dissolution tests to mimic the effects in the stomach were designed for H 2 -receptor antagonists and proton pump inhibitors. Conclusions The impact of ARAs on GI physiology depends on the type, duration and amount of ARA administered as well as the location in the GI tract, with greatest impact on gastric physiology. Whilst ARAs have a high impact on the gastric fluid pH and composition, changes in volume, viscosity, surface tension and gastric emptying appear to be less profound. The proposed dissolution tests enable a ready comparison between dosage form performance in healthy adults and those receiving proton pump inhibitors or H 2 -receptor antagonists.