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Evaluation in pig of an intestinal administration device for oral peptide delivery.
Berg, Staffan; Uggla, Teresia; Antonsson, Malin; Nunes, Sandro Filipe; Englund, Maria; Rosengren, Louise; Fahraj, Masoud; Wu, Xiaoqiu; Govender, Rydvikha; Söderberg, Magnus; Janzén, David; Van Zuydam, Natalie; Hugerth, Andreas; Larsson, Anette; Abrahmsén-Alami, Susanna; Abrahamsson, Bertil; Davies, Nigel; Bergström, Christel A S.
Afiliación
  • Berg S; The Swedish Drug Delivery Center, Department of Pharmacy, Uppsala University, BMC P.O. Box 580, SE-751 23 Uppsala, Sweden; Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg, Sweden.
  • Uggla T; Animal Sciences and Technologies, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • Antonsson M; Animal Sciences and Technologies, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • Nunes SF; Animal Sciences and Technologies, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • Englund M; Drug Metabolism and Pharmacokinetics, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • Rosengren L; Drug Metabolism and Pharmacokinetics, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • Fahraj M; Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg, Sweden.
  • Wu X; Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg, Sweden.
  • Govender R; Oral Product Development, Pharmaceutical Technology & Development, Operations, AstraZeneca Gothenburg, Sweden.
  • Söderberg M; Cardiovascular, Renal and Metabolism Safety, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • Janzén D; Drug Metabolism and Pharmacokinetics, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • Van Zuydam N; Data Science and Quantitative Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • Hugerth A; Ferring Pharmaceuticals A/S, Product Development and Drug Delivery, Global Pharmaceutical R&D, Amager Strandvej 405, 2770 Kastrup, Denmark.
  • Larsson A; Applied Chemistry, Department of Chemistry and Chemical Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden.
  • Abrahmsén-Alami S; Innovation Strategies & External Liasons, Pharmaceutical Technology & Development, Operations, AstraZeneca Gothenburg, Sweden.
  • Abrahamsson B; Oral Product Development, Pharmaceutical Technology & Development, Operations, AstraZeneca Gothenburg, Sweden.
  • Davies N; Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg, Sweden.
  • Bergström CAS; The Swedish Drug Delivery Center, Department of Pharmacy, Uppsala University, BMC P.O. Box 580, SE-751 23 Uppsala, Sweden. Electronic address: christel.bergstrom@farmaci.uu.se.
J Control Release ; 353: 792-801, 2023 01.
Article en En | MEDLINE | ID: mdl-36493948
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Mucosa Intestinal / Intestinos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Suecia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Mucosa Intestinal / Intestinos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Suecia