Illeum targeted semaglutide delivery and pharmacokinetic study in an experimental porcine animal model via oesophagogastroduodenoscopic administration

Abstract

Oral bioavailability of peptides can be improved by targeting specific gastro-intestinal segments, such as the ileum. However, oral drug products with a drug release in the ileum are challenging to develop. The main objectives of this study were: (a) to evaluate imaging technologies for the pig model after endoscopic drug dosing, (b) to evaluate the in vivo targeting properties of a novel coating technology and (c) to measure the impact of GI targeting on the absorption of the GLP-1 agonist semaglutide. The investigational drug product was a capsule containing the contrast agent substance BaSO₄ as well as a tablet containing semaglutide.

Highlights

• Oesophagogastroduodenoscopic administration of a capsule formulation containing BaSO₄ in combination with fluoroscopy allows precise visualization of the start of drug release in the pig model
• The use of an enteric coating combining a pH dependent polymer and a time dependent polymer enables the targeting of the distal part of the small intestine
• Release of semaglutide in the distal part of the small intestine correlates with higher semaglutide plasma levels, compared to a release in the proximal segment

Capsules with different enteric coatings were administered via endoscope into the anesthetized pigs’ duodenum. After regaining consciousness, fluoroscopy was performed in 30 min intervals. This scheme was continued until BaSO₄ release was detected. Animals then were examined via computer tomography scanning. The combination of fluoroscopy and capsules containing BaSO₄ enabled the precise visualization of the start of the release of the capsule content. Detailed determination of the GI localization of drug release via CT was challenging.

The start of the drug release monitored via fluoroscopy was on average after 1 h and 15 min in the group with Eudragit L30D-55 coated capsules (reference group), compared to an average of 4 h 5 min in the group with Cyprumed polymer mixture (combination of pH- and time dependent polymer) coated capsules. Localization of drug release of the Cyprumed coated capsules was the distal part of the small intestine, approximately a few centimeters proximal to the caecum. Comparison of the PK data of the early and late release groups showed that a drug release in the more distal part of the small intestine correlates with higher absorption of semaglutide.

Read more here

Materials

Semaglutide was purchased from Bachem (Bubendorf, Switzerland). Barium sulfate, microcrystalline cellulose (Avicel PH-101) and sodium caprate were bought from Sigma Aldrich, Austria. Water (HPLC grade) and citric acid monohydrate were sourced from VWR, Austria. Sorbitol (Neosorb Psingle bond100C) and magnesium stearate were obtained from Roquette, France. Polymers for enteric coating (Eudragit L30D-55, Eudragit NM30D, Eudragit FS30D) and Plasacryl T20 were purchased from Evonik, Germany.

Michael Blümlinger, Flora Hamar, Martin Werle, Florian Föger, Martina Hrouda, Eberhard Ludewig, Christian Huck, Martin Heiss, Lukas Schwarz, Illeum targeted semaglutide delivery and pharmacokinetic study in an experimental porcine animal model via oesophagogastroduodenoscopic administration, Journal of Controlled Release, 2025, 114164, ISSN 0168-3659, https://doi.org/10.1016/j.jconrel.2025.114164.

Visit our free webinar:

The Right Choice:

Direct Compression Lactose in Drug Development & Sustainability 

WEBINAR REcording HERE