The dynamic gastric environment and its impact on drug and formulation behaviour

Eur J Pharm Sci. 2017 Jan 1;96:207-231. doi: 10.1016/j.ejps.2016.08.060. Epub 2016 Sep 3.

Abstract

Before being absorbed in the small intestine and/or colon, orally administered drugs inevitably need to pass through the stomach. Hence, it seems reasonable that the residence of a dosage form in the gastric environment, however brief it may be, may influence drug disposition further down the gastrointestinal tract and may potentially impact systemic exposure to a drug of interest. However, research efforts in the past mainly focused on drug disposition at the level of the intestine, i.e. the main site of absorption, hereby disregarding or oversimplifying the stomach's contribution to gastrointestinal drug disposition. In the first part of this review, the complexity of the stomach with regard to anatomy, physiology and gastric fluid composition is emphasized. Between-population differences in gastric functioning and physicochemical characteristics of gastric fluids are discussed. The second part of this review focuses on several of the processes to which a dosage form can be exposed during its passage through the stomach and the implications for gastrointestinal drug behaviour and systemic drug disposition. Finally, the influence of real-life dosing conditions on drug disposition is discussed in the context of the stomach.

Keywords: Biopharmaceutics; Drug disposition; Gastrointestinal tract; Oral drug delivery; Stomach.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Animals
  • Chemistry, Pharmaceutical
  • Gastric Emptying / drug effects
  • Gastric Emptying / physiology*
  • Gastric Mucosa / metabolism*
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / metabolism
  • Humans
  • Intestinal Absorption / drug effects
  • Intestinal Absorption / physiology*
  • Pharmaceutical Preparations / administration & dosage
  • Pharmaceutical Preparations / chemistry
  • Pharmaceutical Preparations / metabolism*
  • Stomach / drug effects

Substances

  • Pharmaceutical Preparations