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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00005666naa a2200673 4500
001oai:DiVA.org:uu-481063
003SwePub
008220802s2023 | |||||||||||000 ||eng|
009oai:research.chalmers.se:5ccbf665-2d57-4362-b788-dba72d65fa27
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4810632 URI
0247 a https://doi.org/10.1016/j.jconrel.2022.12.0112 DOI
0247 a https://research.chalmers.se/publication/5339152 URI
040 a (SwePub)uud (SwePub)cth
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Berg, Staffanu Uppsala universitet,Institutionen för farmaci,Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg, Sweden,Uppsala University,AstraZeneca AB4 aut0 (Swepub:uu)stabe945
2451 0a Evaluation in pig of an intestinal administration device for oral peptide delivery
264 1b Elsevier,c 2023
338 a print2 rdacarrier
520 a 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.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmaceutiska vetenskaper0 (SwePub)301012 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Pharmaceutical Sciences0 (SwePub)301012 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmakologi och toxikologi0 (SwePub)301022 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Pharmacology and Toxicology0 (SwePub)301022 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinsk bioteknologix Biomaterialvetenskap0 (SwePub)304032 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Medical Biotechnologyx Biomaterials Science0 (SwePub)304032 hsv//eng
653 a Oral peptide delivery
653 a intestinal administration
653 a sodium caprate
653 a permeation enhancer
653 a MEDI7219
653 a Biofarmaci
653 a Biopharmaceutics
653 a Galenisk farmaci
653 a Pharmaceutics
7001 a Uggla, Teresiau AstraZeneca AB4 aut
7001 a Antonsson, Malinu AstraZeneca AB4 aut
7001 a Nunes, Sandro Filipeu AstraZeneca AB4 aut
7001 a Englund, Mariau AstraZeneca AB4 aut
7001 a Rosengren, Louiseu AstraZeneca AB4 aut
7001 a Fahraj, Masoudu AstraZeneca AB4 aut
7001 a Wu, Xiaoqiuu AstraZeneca AB4 aut
7001 a Govender, Rydvikha,d 1989u AstraZeneca AB4 aut0 (Swepub:cth)rydvika
7001 a Söderberg, Magnusu AstraZeneca AB4 aut
7001 a Janzén, Davidu AstraZeneca AB4 aut
7001 a Van Zuydam, Natalieu AstraZeneca AB4 aut
7001 a Hugerth, Andreas4 aut
7001 a Larsson, Anette,d 1966u Chalmers tekniska högskola,Chalmers University of Technology4 aut0 (Swepub:cth)anettel
7001 a Bergström, Christel A. S.,d 1973-u Uppsala universitet,Institutionen för farmaci4 aut0 (Swepub:uu)cjo29958
7001 a Abrahamsson, Bertilu AstraZeneca AB4 aut
7001 a Davies, Nigelu AstraZeneca AB4 aut
7001 a Bergström, Christel A. S.,d 1973-u Uppsala universitet,Institutionen för farmaci4 aut0 (Swepub:uu)cjo29958
7102 a Uppsala universitetb Institutionen för farmaci4 org
7730 t Journal of Controlled Released : Elsevierg 353, s. 792-801q 353<792-801x 0168-3659x 1873-4995
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-481063
8564 8u https://doi.org/10.1016/j.jconrel.2022.12.011
8564 8u https://research.chalmers.se/publication/533915

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