Does the appearance of the Magenstrasse depend on the amount of water consumed?

Abstract

The Magenstrasse (stomach road) is a phenomenon describing the rapid evacuation of water drunken after a solid meal from the stomach. So far, its existence has been demonstrated for water volumes of 150 mL or more. The aim of this three-arm, randomised, cross-over, 12-subject study was to investigate whether the Magenstrasse is also present for smaller water volumes. For this purpose, gastric emptying of 50, 100 or 150 mL of water that was administered after a light meal was determined using MR imaging. With each dose of water, a fast-dissolving compression coated tablet containing caffeine and iron oxide as well as a hard capsule containing stable isotope labelled caffeine and medium-chain triglycerides were administered. This made it possible to determine the initial localization of the respective forms in the stomach on MR images as a function of the amount of water drunk, and also to determine the emptying rates of the two caffeine variants using saliva samples that were obtained in the study and quantified using LC-MS/MS. Gastric emptying of the ingested water was rapid and usually completed after approximately 20 min, regardless of the applied volume. In contrast to the consumed water, gastric emptying of natural caffeine and stable isotope labelled caffeine was delayed. The capsule usually floated on liquid and chyme, whereas the compression coated tablet was often embedded in chyme.

Introduction

The Magenstrasse or stomach road describes the phenomenon of rapid emptying of water from the stomach in the postprandial state (Grimm et al., 2017). This emptying occurs mainly along the entire stomach wall or the Plicae Gastricae of the lesser curvature towards the antrum, pylorus and finally into the duodenum as studies in humans and dogs have shown (Koziolek et al., 2014; Jefferson, 1915; Scheunert, 1912; Malagelada et al., 1979; Malagelada, 1977; Almutairi et al., 2023; Kiyota et al., 2022a; Koziolek et al., 2016). Another mechanism involved could be an adaptive relaxation of the stomach wall with increasing wall tension and hydrostatic pressure of the applied fluid volume (Grimm et al., 2017). Due to the positioning of orally applied dosage forms in the stomach and their resulting contact time with dissolution or liberation media, the Magenstrasse is thought to have a significant influence on the variability of drug absorption in the postprandial state and may therefore influence plasma levels (Koziolek et al., 2016; Weitschies et al., 2005; Weitschies et al., 2008). For bioavailability and bioequivalence studies under fasting and fed conditions FDA (US Food & Drug Administration) guidances recommend drug administration together with 240 mL of water, EMA (European Medicines Agency) advices at least 150 mL of water (FDA, 2002; EMA, 2010; FDA, 2003).

However, real-life dosing conditions often differ from the amounts prescribed in the guidelines. Hens et al. describe for a Dutch population that most people take their medication with only half a glass of water (100–120 mL). In fact, the second most reported intake volume was only a sip of water (Hens et al., 2017). This is supported with a recent study by Sarwinska et al. for a northern German population of elderly people. Most subjects took their medication with 100–200 mL of water and 21 % with just a few sips (about 50 mL) (Sarwinska et al., 2024).

It has been shown that the gastric emptying rates of 20, 50 and 240 mL of water consumed under fasting conditions are well comparable (Grimm et al., 2023a; Grimm et al., 2023b). Based on the assumed mechanisms underlying the stomach road, the question arises as to whether there is a lower volume limit for the development of the stomach road. The aim of the present study was therefore to investigate whether the Magenstrasse also occurs when drinking volumes of water of 50, 100 and 150 mL. In an MRI (magnetic resonance imaging) study in healthy volunteers, the stomach volume was to be determined after eating a test meal and drinking 50 mL, 100 mL and 150 mL of water.

Furthermore, by using caffeine as a saliva marker, the influence of the drinking volume and the site of disintegration in the stomach of rapidly disintegrating dosage forms taken with water was to be investigated. The dosage forms used were gelatine hard capsules filled with 25 mg 13C3-caffeine and compression-coated tablets containing 25 mg regular caffeine (Tzakri et al., 2023). Both dosage forms included a compartment with an MR identifiable marker substance to locate them in the stomach.

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Materials & Methods

Compression-coated tablets were manufactured as described elsewhere (Tzakri et al., 2023). Briefly, the inner core contains regular caffeine and black iron oxide and the outer coating acts as a rapidly disintegrating protective layer for the core. This is intended to prevent caffeine contamination of the oral cavity during the swallowing process. The iron oxide in the core was used for visualisation in the MR images by means of the characteristic susceptibility artefact that is visible in the used MRI sequences. The components of the tablet are given in Table 1. The tablets were biconvex-shaped and had a diameter of 9 mm and a hight of 5 mm. Tablet hardness, mass uniformity and in vitro disintegration and dissolution tests were in line with the results of Tzakri et al. (Tzakri et al., 2023). The compression-coated tablet had an approximate density of 1.18 g/mL.

Table 1. Composition of the compression-coated tablets.

Linus Großmann, Johanna Cyrus, Stefan Senekowitsch, Toni Wildgrube, Theodora Tzakri, Marie-Luise Kromrey, Werner Weitschies, Michael Grimm, Does the appearance of the Magenstrasse depend on the amount of water consumed?, International Journal of Pharmaceutics: X, Volume 10, 2025, 100365, ISSN 2590-1567, https://doi.org/10.1016/j.ijpx.2025.100365.

Read also our introduction article on Capsule here: