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Experiences and Tra...
Experiences and Translatability of In Vitro and In Vivo Models to Evaluate Caprate as a Permeation Enhancer
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- Emeh, Prosper (författare)
- Uppsala universitet,Institutionen för farmaci
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- Breitholtz, Katarina (författare)
- AstraZeneca, Drug Metab & Pharmacokinet, Res & Early Dev, Cardiovasc Renal & Metab,BioPharmaceut R&D, SE-43183 Gothenburg, Sweden.
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- Berg, Staffan (författare)
- AstraZeneca, Adv Drug Delivery, Pharmaceut Sci, R&D, SE-43183 Gothenburg, Sweden.
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- Vedin, Charlotta (författare)
- AstraZeneca, Drug Metab & Pharmacokinet, Res & Early Dev, Cardiovasc Renal & Metab,BioPharmaceut R&D, SE-43183 Gothenburg, Sweden.
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- Englund, Maria (författare)
- AstraZeneca, Drug Metab & Pharmacokinet, Res & Early Dev, Cardiovasc Renal & Metab,BioPharmaceut R&D, SE-43183 Gothenburg, Sweden.
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- Uggla, Teresia (författare)
- AstraZeneca, BioPharmaceut R&D, Clin Pharmacol & Safety Sci, Lab Anim Sci, SE-43183 Gothenburg, Sweden.
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- Antonsson, Malin (författare)
- AstraZeneca, BioPharmaceut R&D, Clin Pharmacol & Safety Sci, Lab Anim Sci, SE-43183 Gothenburg, Sweden.
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- Nunes, Filipe (författare)
- AstraZeneca, BioPharmaceut R&D, Clin Pharmacol & Safety Sci, Lab Anim Sci, SE-43183 Gothenburg, Sweden.
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- Hilgendorf, Constanze (författare)
- AstraZeneca, Drug Metab & Pharmacokinet, Res & Early Dev, Cardiovasc Renal & Metab,BioPharmaceut R&D, SE-43183 Gothenburg, Sweden.
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- Bergström, Christel A. S. (författare)
- Uppsala Univ, Swedish Drug Delivery Ctr, Dept Pharm, SE-75123 Uppsala, Sweden.
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- Davies, Nigel (författare)
- AstraZeneca, Adv Drug Delivery, Pharmaceut Sci, R&D, SE-43183 Gothenburg, Sweden.
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(creator_code:org_t)
- American Chemical Society (ACS), 2024
- 2024
- Engelska.
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 21:1, s. 313-324
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Transient permeation enhancers (PEs) have been widely used to improve the oral absorption of macromolecules. During pharmaceutical development, the correct selection of the macromolecule, PE, and the combination needs to be made to maximize oral bioavailability and ensure successful clinical development. Various in vitro and in vivo methods have been investigated to optimize this selection. In vitro methods are generally preferred by the pharmaceutical industry to reduce the use of animals according to the "replacement, reduction, and refinement" principle commonly termed "3Rs," and in vitro methods typically have a higher throughput. This paper compares two in vitro methods that are commonly used within the pharmaceutical industry, being Caco-2 and an Ussing chamber, to two in vivo models, being in situ intestinal instillation to rats and in vivo administration via an endoscope to pigs. All studies use solution formulation of sodium caprate, which has been widely used as a PE, and two macromolecules, being FITC-dextran 4000 Da and MEDI7219, a GLP-1 receptor agonist peptide. The paper shares our experiences of using these models and the challenges with the in vitro models in mimicking the processes occurring in vivo. The paper highlights the need to consider these differences when translating data generated using these in vitro models for evaluating macromolecules, PE, and combinations thereof for enabling oral delivery.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- transient permeation enhancer
- sodium caprate
- oral peptide delivery
- Ussing chamber
- Caco-2
- intestinal bolus instillation
- in vitro-in vivotranslatability
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Emeh, Prosper
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Breitholtz, Kata ...
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Berg, Staffan
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Vedin, Charlotta
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Englund, Maria
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Uggla, Teresia
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Antonsson, Malin
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Nunes, Filipe
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Hilgendorf, Cons ...
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Bergström, Chris ...
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Davies, Nigel
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