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Title [sv]
En tredimensionell in vitro modell av magtarmkanalen för att möjliggöra rationell utveckling av oralt administrerade läkemedel
Title [en]
A three dimensional in vitro model of the gut to inform on optimal dosage form design for oral drug delivery
Abstract [en]
The vast majority of modern pharmacologically active compounds demands advanced drug delivery systems (ADDSs) to be developed as orally administered medicines. The goal for this project is to design lab bench models of the gut that can assess performance of ADDSs. A small intestinal-like absorption membrane will be designed by cell engineering with focus on incorporating transport proteins of importance for absorption of drugs. These cells will be explored for their potential to form small intestine-like tubes by making use of 3D printing and microfluidics. When the small intestine is established it will be coupled to similar models of the large intestine to allow regional differences, flow rates and transit times to inform on the performance of the ADDS. Finally, the system will be investigated for its potential use as disease models, herein exemplified with inflammatory bowel disease. All steps will be validated with drug-like molecules (small molecules) and biological drugs presented in ADDS of different types. When the objectives of the project are fulfilled, dynamic models for lab bench assessment of ADDS are designed where the interplay between release, dissolution, solubility, in vivo digestion and permeation is studied simultaneously. The models will provide insights into potential differences between patients, laying a platform for in vitro assessment of formulated personalized medicines such as dosage forms requiring local delivery to the colon.
Publications (1 of 1) Show all publications
Sinko, P. D., Parker, L., Prahl Wittberg, L. & Bergström, C. A. S. (2024). Estimation of the concentration boundary layer adjacent to a flat surface using computational fluid dynamics. International Journal of Pharmaceutics, 653, Article ID 123870.
Open this publication in new window or tab >>Estimation of the concentration boundary layer adjacent to a flat surface using computational fluid dynamics
2024 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 653, article id 123870Article in journal (Refereed) Published
Abstract [en]

Dissolution-permeation (D/P) experiments are widely used during preclinical development due to producing results with better predictability than traditional monophasic experiments. However, it is difficult to compare absorption across in vitro setups given the propensity to only report apparent permeability. We therefore developed an approach to predict the concentration boundary layer for any D/P device by using computational fluid dynamics (CFD). The Navier-Stokes and continuity equation in 2D were solved numerically in MATLAB and by finite element methods in COMSOL v6.1 to predict the momentum (ηf′) and concentration (ηg) boundary layer for a flow over a flat plate, i.e. the classical Blasius boundary layer flow. A MATLAB algorithm was developed to calculate the edge of either boundary layer. The methodology to determine the concentration boundary layer based on Blasius’s analysis provided an accurate estimate for both ηf′ and ηg, resulting in, ηf′/ηg, at high Schmidt numbers (Sc ∼ 1000) within 14 % of the Blasius solution and 6.6 % of the accepted Schmidt number correlation (Sc1/3=ηf′/ηg). The methodology based on the Blasius analysis of the concentration boundary layer using velocity and concentration profiles computed using CFD presented herein will enable characterization/analysis of complex D/P apparatuses used in preclinical development, where an analytical solution may not be available.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
Computational fluid dynamics, Concentration boundary layer, Aqueous boundary layer, Absorption, Simulation, Dissolution, Permeation
National Category
Fluid Mechanics
Identifiers
urn:nbn:se:uu:diva-527233 (URN)10.1016/j.ijpharm.2024.123870 (DOI)001202183900001 ()38401511 (PubMedID)
Funder
Swedish Research Council, 2018-03281
Available from: 2024-04-30 Created: 2024-04-30 Last updated: 2025-02-09Bibliographically approved
Principal InvestigatorBergström, Christel
Coordinating organisation
Uppsala University
Funder
Period
2019-01-01 - 2022-12-31
National Category
Pharmaceutical SciencesCell and Molecular BiologyMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
DiVA, id: project:6252Project, id: 2018-03281_VR