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. Three project phases are 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) Particle velocimetry and diffusion-absorption experiments to validate CFD hydrodynamics predictions. Phase 1 will be time intensive as time dependent CFD must be evaluated to identify the most reasonable geometry for the flow through channel as well as a range of operating conditions. We hope to have access to high power local computers, the UPPMAX Rackham supercomputer cluster at Uppsala University, and a leader in the field of CFD as an adjunct faculty. We will take existing literature parameters for the geometry of the major intestinal segments and 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. Phase 2 fabrication and automation is possible at Biomedinskt Centrum.
We will also 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. This is accomplished by looking at the shear profile and connecting dynamic viscosity data already generated to predict diffusivity in the bulk fluid as well as at the diffusion boundary layer in these devices. The results of this part of the study will feed directly into the design of the microfluidic device. Ultimately, both simulation efforts are hoped to yield a more realistic design space for the human mimicking bench top device we are trying to build.