(W1030-12-79) In Vivo Evaluation of the Enteric Properties of Capsugel® Enprotect® Capsules in Fed State Conditions

Purpose: A large range of therapeutic molecules are sensitive to the acidity and/or enzymes of the gastric environment and must be formulated as enteric dosage forms to be dosed orally. To facilitate the development of these dosage forms, ready-to-use Capsugel® Enprotect® capsule was launched in 2022 after confirming its ability to protect encapsulated proteins from acid and enzymatic degradation [1]. The enteric properties of this capsule were validated in vivo in fasted healthy volunteers by two complementary methods which both confirmed that capsules disintegrated in the distal small intestine regardless of the gastric residence time [2]. The present study aims to evaluate if the enteric properties of Capsugel® Enprotect® capsules are maintained in vivo in fed state conditions.

Methods: excipients, ¹³C-caffeine and iron oxide. One filled capsule was administered orally with 240 mL of water in upright position to each of the 16 healthy volunteers in postprandial state, 30 minutes after intake of a standard breakfast (2 slices of toast, 30 g strawberry jam, 150 mL orange juice, 250 g fruit yogurt (low fat)). Similarly as for the in vivo evaluation in fasted state, the localization and time for the capsules to disintegrate in fed state conditions were evaluated by two independent methods: magnetic resonance imaging (MRI) and detection of caffeine in saliva. Saliva samples were collected one minute after every MRI-measurement in intervals of 15 minutes up to 480 minutes after capsule intake, to confirm capsule integrity or opening and release of its content.

Results: MRI observations indicated longer gastric residence times in the fed state compared to previous fasted state study. However, even with extended residence time at increased pH and in the presence of higher mechanical forces in fed state, MRI observations also confirmed that no capsules opened in the stomach of the volunteers. These observations were corroborated by caffeine appearance in saliva which was only detected when capsules were located in small intestine. Both detection methods indicated that gastric residence time had no influence on the intestinal disintegration time.

Conclusion: Capsugel® Enprotect® capsules retain their enteric properties in vivo in fed state conditions.

References: [1] V. Jannin, C. Duysburgh, V. Gonzalez, M. Govaert, M. Agisson, M. Marzorati, N. Madit, In vitro evaluation of the gastrointestinal delivery of acid-sensitive pancrelipase in a next generation enteric capsule using an exocrine pancreatic insufficiency disease model, International Journal of Pharmaceutics. 630 (2023) 122441. https://doi.org/10.1016/j.ijpharm.2022.122441.
[2] A. Rump, M.-L. Kromrey, E. Scheuch, V. Jannin, L. Rehenbrock, M.V. Tzvetkov, W. Weitschies, M. Grimm, In Vivo Evaluation of a Gastro-Resistant HPMC-Based “Next Generation Enteric” Capsule, Pharmaceutics. 14 (2022) 1999. https://doi.org/10.3390/pharmaceutics14101999.