SUPR
A flexible, multicompartment flow through dissolution and absorption in vitro model designed with human in vivo hydrodynamic parameters
Dnr:

NAISS 2024/22-180

Type:

NAISS Small Compute

Principal Investigator:

Patrick Sinko

Affiliation:

Uppsala universitet

Start Date:

2024-03-01

End Date:

2025-03-01

Primary Classification:

30101: Pharmaceutical Sciences

Webpage:

Allocation

Abstract

The majority of new drug candidates are poorly soluble and highly permeable, making conventional in vitro testing nearly obsolete. It is imperative to implement an animal-free, physiologically relevant benchtop test that allows pharmacists to design next generation drug products. New in vitro models will be established for the intestinal tract (GIT) by using computational fluid dynamic simulations (CFD) and microfluidic devices to mimic GIT dynamics (pH gradient, permeation, transit times, antero/retrograde flow, surface area to volume ratio, and hydrodynamics). The in vitro device will assess advanced orally ingested drug delivery systems and will be able to utilize both artificial and biological membrane models. Project phases include 1) CFD based design of the basic module to biomimic the gastrointestinal tract segments 2) Fabrication of the basic module and setup of the control systems 3) 3D printing of the device and incorporating cell membrane for iterative design refinements. We hope to have access to high power local computers, the UPPMAX Rackham supercomputer cluster at Uppsala University, and a have an established collaboration with Lisa Prahl Wittberg at KTH. We will take existing literature parameters and the results from my PhD students 1 published paper and his 2nd manuscript (in draft) to inform the design of the geometry of the major intestinal segments. Then vary the geometric constants of the channel to understand the range of the design space that covers both fasting and fed state mechanical stresses with different types of input flow. Fabrication of the device based on the CFD studies will happen at the UPRINT facilities at Biomedinskt Centrum. To gain an understanding of the dynamics that the mucusal layer plays in the human GI environment and how it will effect the simulations in the device are designing, we will simulation a mucus perfusion chamber in order to generate data regarding drug transport through the mucus. We will continue a project started in 2023 that helped develop the tools required to build the VR-3R device. This project focuses on the simulation of microfluidic devices for the purposed of implementing microfluidic chips to study biological processes influence on nanomedicines. We will also continue to investigate the flow behavior of 3 devices currently used during in vitro evaluation of new drug products. This modeling will allow for direct comparisons of the mass transport behavior in each system in order to create a better understanding of how to compare each system in the context of dissolution and absorption performance.