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The aim of the present study was to investigate the gastroretentive capacity of different formulation principles. This was indirectly determined by the absorption behavior of caffeine from the dosage forms. A slow and continuous appearance of caffeine in the saliva of healthy volunteers was used as a parameter for a prolonged gastric retention time. For this purpose, a four-way study was conducted with twelve healthy volunteers using the following test procedures: (1) Effervescent granules with 240 mL of still water administered in fed state, (2) effervescent granules with 20 mL of still water in fed state, (3) extended release (ER) tablet with 240 mL of still water in fed state, and (4) effervescent granules with 240 mL of still water in fasted state. The initial rise of the caffeine concentrations was more pronounced after the intake of the effervescent granules in the fed state compared to that of the ER tablets. However, t max tended to be shorter in the fed study arms following administration of the ER tablet compared to the granules. Overall, the application of active pharmaceutical ingredients formulated as effervescent granules seems to be a promising approach to increase their gastric residence time after intake in fed state., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maximilian Feldmüller was an employee of the University of Greifswald during his contribution to this work and is now an employee of Bayer. Mirko Koziolek was an employee of the University of Greifswald during his contribution to this work and is now an employee of Abbvie., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Gastrointestinal fluid volumes are a crucial parameter for dissolution and absorption of orally taken medications. Most often 240 mL are used in clinical standard setups. Nonetheless, surveys in patient populations revealed dramatically lower volumes for intake of oral medications in real life and even in some clinical studies reduced fluid volumes are common. These reductions might have serious impact on pharmacokinetics. Thus, it was the aim of this study to compare the gastric emptying of 240 mL and 20 mL of water in 8 healthy volunteers. For investigation of gastric fluid volumes Magnetic Resonance Imaging with strongly T2 weighted sequences was used. Gastric emptying was additionally quantified via caffeine pharmacokinetics measured in saliva. The absolute gastric volumes after intake of 240 mL or 20 mL obviously differed by factor 10 but relative gastric emptying expressed as fraction per time was nearly comparable. Only slighter slower emptying after intake of 20 mL was observed. Salivary caffeine pharmacokinetics representing mass transfer from stomach to small intestine after intake of different volumes did not differ. The absorbed caffeine fraction and emptied gastric volume fraction correlated well after intake of 240 mL, but not after intake of 20 mL, indicating a higher influence of secretion on gastric volume measurements after intake of smaller volumes. Relative gastric emptying as measured with MRI and salivary caffeine method was only slightly delayed, thus transfer of orally administered drug fraction could be comparable even with lower fluid intake as can be seen by comparable caffeine pharmacokinetics. Nonetheless, the considerably reduced volumes might interfere with dissolution and absorption., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Gastric water emptying as a critical parameter for oral drug absorption can be investigated by several imaging techniques or by the interpretation of pharmacokinetics of appropriate substances. Recently introduced salivary caffeine kinetics is a valuable tool, but the required caffeine abstinence limits its applicability. To avoid the caffeine abstinence, stable isotope-labeled caffeine might be used, but the representability and transferability of kinetics for evaluation of gastric emptying must be demonstrated. Thus, salivary caffeine pharmacokinetics were compared for naturally occurring 12C-caffeine and 13C3-caffeine after the administration of water under fasting conditions in six healthy young subjects. For this purpose, an ice capsule containing the two caffeine species was administered with 50 mL tap water. Gastric water emptying was simultaneously quantified using magnetic resonance imaging (MRI). Gastric emptying of 50 mL of water could be successfully evaluated. The salivary caffeine kinetics of 13C3- and 12C-caffeine were nearly congruent and showed good linear correlations in all subjects, with a mean correlation coefficient of 0.96 in pooled data. Thus, the substitution of natural 12C caffeine with stable isotope-labeled 13C3-caffeine offers the opportunity for broader application of the salivary caffeine gastric emptying technique and increases the robustness of the method against environmental contamination with caffeine. [ABSTRACT FROM AUTHOR]

Many orally dosed APIs are bioavailable only when formulated as an enteric dosage form to protect them from the harsh environment of the stomach. However, an enteric formulation is often accompanied with a higher development effort in the first place and the potential degradation of fragile APIs during the coating process. Ready-to-use enteric hard capsules would be an easily available alternative to test and develop APIs in enteric formulations, while decreasing the time and cost of process development. In this regard, Lonza Capsugel® Next Generation Enteric capsules offer a promising approach as functional capsules. The in vivo performance of these capsules was observed with two independent techniques (MRI and caffeine in saliva) in eight human volunteers. No disintegration or content release in the stomach was observed, even after highly variable individual gastric residence times (range 7.5 to 82.5 min), indicating the reliable enteric properties of these capsules. Seven capsules disintegrated in the distal part of the small intestine; one capsule showed an uncommonly fast intestinal transit (15 min) and disintegrated in the colon. The results for this latter capsule by MRI and caffeine appearance differed dramatically, whereas for all other capsules disintegrating in the small intestine, the results were very comparable, which highlights the necessity for reliable and complementary measurement methods. No correlation could be found between the gastric residence time and disintegration after gastric emptying, which confirms the robust enteric formulation of those capsules. [ABSTRACT FROM AUTHOR]