Interests of the ‘artifical stomach’ techniques to study antacid formulations: Comparison with in vivo evaluation

Abstract

In this overview, the methods for assessing antacid activity in vitro are surveyed, and the problems of their comparison with in vivo methods of evaluation are discussed. In vitro assessment is based on two types of method: static and dynamic. The static method of titration, with end-of-titration pH values ranging between 3.0 and 1.0, has been used to quantify the number of sites capable of binding H+ ions at each end-of-titration pH, and to identify certain chemical mechanisms involved in this binding; in other words, this approach provides the pharmacological characteristics of the drugs tested. In contrast, it does not take into account physiological factors modulating antacid activity, such as gastroduodenal fluxes (including gastric emptying), drug adherence to the mucosa, and acid secretion. The dynamic method was initially based on an artificial stomach model, which has gradually been upgraded to a computer-controlled artificial stomach-duodenum model. This model overcomes certain weaknesses of the static method by simulating flux and pH conditions in the gastroduodenal tract, by taking into account interactions with the gastric mucosa and thereby reproducing the in vivo medium encountered by antacids. It is therefore capable of reflecting the characteristics of antacids, namely their effect on gastric pH and resistance to acidification, at the same time helping to identify the underlying chemicophysical mechanisms. In vivo, the antacid effect can be assessed qualitatively by means of pH-meter studies in healthy volunteers, both in baseline conditions and during secretory stimulation, and also quantitatively by methods based on intragastric titration in response to a liquid meal (IGT). pH-meter studies in baseline conditions come up against the variability of the basal pH and antacid homogenization with gastric contents, which results in a wide range of individual values. This variability is found in pH-meter studies during pentagastrin infusion and, to a lesser degree, in response to a meal. Close correlations have, however, been established between results obtained with the artificial stomach model and in healthy volunteers submitted to pH-metric or IGT studies, with several antacids. It seems that the artificial stomach method is sufficiently reproducible to make it the method of choice for investigating the antacid activity of all drugs aimed at treating acid hypersecretion disorders. In contrast, in vivo studies may be warranted for precise therapeutic indications, such as treatment of duodenal ulcer or gastro-esophageal reflux, in which the therapeutic effect is judged on the basis of an improvement in symptoms and endoscopic criteria, without the need to demonstrate the antacid effect itself.

Current Evidence on the Bioavailability of Food Bioactive Peptides

“…The main bi-compartmental models simulate the luminal conditions of the stomach and proximal small intestine. Based on in vivo data, these computer controlled systems reproduce the temperature, pH changes in the gastric and duodenal compartments, gastric emptying, pepsin, pancreatic juice and/or bile salts content [ 64 , 65 ], and dialysis of digestion end products [ 66 ].…”

Recommendations of the Russian Gastroenterological Association in Diagnosis and Treatment of Gastroesophageal Reflux Disease

“…Антацидные средства -алюминия фосфат 2,08 г, комбинированные препараты -магалдрат 400 или 800 мг и симетикон 20 или 40 мг, алюминия гидроксид 400 мг и магния гидроксид 400 мг применяют в лечении умеренно выраженных и нечасто возникающих симптомов, особенно тех, которые связаны с несоблюдением рекомендованного образа жизни [124,[126][127][128].…”

In Vitro, in Silico, and in Vivo Assessments of Intestinal Precipitation and Its Impact on Bioavailability of a BCS Class 2 Basic Compound

“…The phenomena of drug supersaturation and precipitation due to pH and solubility changes have been studied extensively in in vitro studies under various mixing and fluid transfer conditions. − In vitro precipitation was found to be affected by the starting concentration, degree of supersaturation, transfer rate, hydrodynamics, and presence of particles. − Several multicompartmental systems that include a gastric compartment and at least one intestinal compartment have been developed, such as artificial stomach and duodenum (ASD), − gastric intestinal simulator (GIS), − and TNO gastrointestinal model (TIM-1) . ASD and GIS measure drug concentration in the intestinal compartment where precipitation may occur.…”