Revolutionising relative bioavailability testing: Using AI-PAT to eliminate animal models

The award will allow Hannah to purchase of a novel probe system capable of real-time monitoring within the lumen of the gastrointestinal tract that can be used with in vitro and machine learning approaches to help predict the oral bioavailability and performance of new drugs, replacing the use of some animal studies for formulation and bioavailability purposes. The University of Strathclyde will be the first institute outside of industry to have access to the probe, which will be made widely available to the community.

This award was made as part of the 2024 non-animal methods infrastructure grants supported with funding from the Department for Science, Innovation and Technology (DSIT).

Our goal is to replace the use of animals in drug relative bioavailability studies by integrating an in-line multifunctional probe (Process Analytical Technology, PAT) into the TIM-1, a state-of-the-art Artificial Intestinal (AI) system, AI-PAT.

Context: Drug product development is a lengthy and complex process that frequently relies on animal testing for relative bioavailability studies where it is essential to understand:

• Their performance in the intestine (solubility, precipitation, bioaccessibility).
• How this performance varies with formulation changes or differences in patient populations (e.g. health vs. disease states).

The state-of-the-art TIM-1 system is the most advanced in vitro system for biorelevant gastrointestinal dissolution testing and prediction of drug bioavailability.1 This system reliably simulates the dynamic environment of the human gastrointestinal tract.

Recently, there has been a rise in the development of poorly soluble drug molecules for various therapeutic applications. These molecules often require enabled formulations that temporarily enhance solubility in the intestinal environment to facilitate absorption but, they are prone to precipitation within the luminal environment, affecting their bioavailability. Crucially, there are currently no in vitro models that can assess the real-time precipitation of oral products.

3Rs challenge: Historically animal studies have been used to assess the relative bioavailability of oral formulations despite knowledge that animals, particularly mice and rats, do not accurately predict gastrointestinal conditions due to interspecies differences. Moreover, these in vivo studies are very limited in terms of what can be learned about drug bioavailability as animal intestinal environments cannot be accessed or closely controlled in real-time. AI-PAT aims to solve these problems and, as a National Facility, will enable researchers across the UK and beyond to evaluate oral product performance in a more thorough and translatable manner, thus replacing the use of animals in this process.

Aims and Objectives: The PAT multifunctional probe will gather detailed data in real time from within the luminal environment, measuring multiple parameters, including precipitation, under various controlled conditions. This data will serve two main purposes:

1. Enhanced understanding of the gastrointestinal performance of the specific formulation under investigation.
2. Contribute to the development of a comprehensive database to underpin machine-learning technology making AI-PAT the “gold-standard” model for testing oral drug bioavailability and animal testing.

Applications and benefits: The open-access AI-PAT facility will offer researchers in academia and industry a unique innovative resource not currently available elsewhere to facilitate better drug development processes and foster innovation while replacing and reducing animal testing.