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

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. 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.