Fed-state gastric media and drug analysis techniques: Current status and points to consider

Abstract

Gastric fed state conditions can have a significant effect on drug dissolution and absorption. In vitro dissolution tests with simple aqueous media cannot usually predict drugs' in vivo response, as several factors such as the meal content, the gastric emptying and possible interactions between food and drug formulations can affect drug's pharmacokinetics. Good understanding of the effect of the in vivo fed gastric conditions on the drug is essential for the development of biorelevant dissolution media simulating the gastric environment after the administration of the standard high fat meal proposed by the FDA and the EMA in bioavailability/bioequivalence (BA/BE) studies. The analysis of drugs in fed state media can be quite challenging as most analytical protocols currently employed are time consuming and labour intensive. In this review, an overview of the in vivo gastric conditions and the biorelevant media used for their in vitro simulation are described. Furthermore an analysis of the physicochemical properties of the drugs and the formulations related to food effect is given. In terms of drug analysis, the protocols currently used for the fed state media sample treatment and analysis and the analytical challenges and needs emerging for more efficient and time saving techniques for a broad spectrum of compounds are being discussed.

Retentive drug delivery systems based on shape memory materials

“…The pyloric sphincter regulates the passage of gastric contents (chyme) into the duodenum. The stomach is especially involved in dietary protein breakdown, secreting pepsinogen, and hydrochloric acid that provides the acidic pH required for enzyme activation . Fat digestion and absorption of certain substances, in addition to water and electrolytes, are also performed.…”

“…Extended gastric release would also provide a ploy to enable formulation as prolonged‐release oral dosage forms of drug substances that, on account of a short elimination half‐life and/or issues of peak‐to‐trough fluctuations in their plasma levels, would constitute ideal candidates yet fail to meet the basic requirement of distal intestinal absorption. The stomach, however, poses harsh and extremely variable conditions, owing to the highly acidic pH and the presence of digestive enzymes as well as of food, source of possible detrimental drug interactions . Active substances that do not possess adequate stability and solubility characteristics in the gastric environment, or may cause damage to the mucosal lining, such as typically antiinflammatory drugs, would not be eligible for release into the stomach.…”

Effects of Biorelevant Media Components on Dissolution Behaviour of 1,2,4‐Thiadiazole Derivative Designed for Alzheimerʼs Disease Prevention

“…Moreover, media simulating the human gastrointestinal tract fluids are commonly used and an approach mimicking laboratory animalsʼ gastrointestinal tract fluids would impact on the preclinical stage of development . To this end, biorelevant media simulating the gastrointestinal conditions in humans were developed and used . There are several media which have been proposed for simulation of the content of stomach and small intestine .…”

“…[5] To this end, biorelevant media simulating the gastrointestinal conditions in humans were developed and used. [3][5] [6] There are several media which have been proposed for simulation of the content of stomach and small intestine. [7] [8] For stomach, the simplest dissolution medium is the Simulated Gastric Fluid (SGF) consisting of sodium dodecyl sulfate, which is used to reduce the surface tension.…”

Evolution of Choice of Solubility and Dissolution Media After Two Decades of Biopharmaceutical Classification System

“…High-purity grades of bile salts are expensive. Additionally, they pose an analytical challenge due to their complex composition and require timeconsuming and complicated procedures (98). However, at this time point, biorelevant media as described above seem to be the best starting point to estimate in vivo solubility and estimate in vivo dissolution behavior of poorly soluble drugs.…”