Evaluation in pig of an intestinal administration device for oral peptide delivery
Journal article, 2023

The bioavailability of peptides co-delivered with permeation enhancers following oral administration remains low and highly variable. Two factors that may contribute to this are the dilution of the permeation enhancer in the intestinal fluid, as well as spreading of the released permeation enhancer and peptide in the lumen by intestinal motility. In this work we evaluated an Intestinal Administration Device (IAD) designed to reduce the luminal dilution of drug and permeation enhancer, and to minimize movement of the dosage form in the intestinal lumen. To achieve this, the IAD utilizes an expanding design that holds immediate release mini tablets and places these in contact with the intestinal epithelium, where unidirectional drug release can occur. The expanding conformation limits movement of the IAD in the intestinal tract, thereby enabling drug release at a single focal point in the intestine. A pig model was selected to study the ability of the IAD to promote intestinal absorption of the peptide MEDI7219 formulated together with the permeation enhancer sodium caprate. We compared the IAD to intestinally administered enteric coated capsules and an intestinally administered solution. The IAD restricted movement of the immediate release tablets in the small intestine and histological evaluation of the mucosa indicated that high concentrations of sodium caprate were achieved. Despite significant effect of the permeation enhancer on the integrity of the intestinal epithelium, the bioavailability of MEDI7219 was of the same order of magnitude as that achieved with the solution and enteric coated capsule formulations (2.5–3.8%). The variability in plasma concentrations of MEDI7219 were however lower when delivered using the IAD as compared to the solution and enteric coated capsule formulations. This suggests that dosage forms that can limit intestinal dilution and control the position of drug release can be a way to reduce the absorptive variability of peptides delivered with permeation enhancers but do not offer significant benefits in terms of increasing bioavailability.

Permeation enhancer

MEDI7219

Intestinal administration

Oral peptide delivery

Sodium caprate

Author

Staffan Berg

Uppsala University

AstraZeneca AB

Teresia Uggla

AstraZeneca AB

Malin Antonsson

AstraZeneca AB

Sandro Filipe Nunes

AstraZeneca AB

Maria Englund

AstraZeneca AB

Louise Rosengren

AstraZeneca AB

Masoud Fahraj

AstraZeneca AB

Xiaoqiu Wu

AstraZeneca AB

Rydvikha Govender

AstraZeneca AB

Magnus Söderberg

AstraZeneca AB

David Janzén

AstraZeneca AB

Natalie Van Zuydam

AstraZeneca AB

Andreas Hugerth

Ferring Pharmaceuticals AS

Anette Larsson

Chalmers, Chemistry and Chemical Engineering, Applied Chemistry

Susanna Abrahmsén-Alami

AstraZeneca AB

Bertil Abrahamsson

AstraZeneca AB

Nigel Davies

AstraZeneca AB

Christel A.S. Bergström

Uppsala University

Journal of Controlled Release

01683659 (ISSN) 18734995 (eISSN)

Vol. 353 792-801

Subject Categories

Pharmaceutical Sciences

Pharmacology and Toxicology

Biomaterials Science

DOI

10.1016/j.jconrel.2022.12.011

PubMed

36493948

More information

Latest update

1/2/2023 2