Title: Gastrointestinal bioreactor to evaluate ingestible medicines and inform formulation and manufacture
Funder: Engineering and Physical Sciences Research Council

Abstract: One of the major factors limiting understanding the complex dynamic environment in the gut, is the technical difficulty of accessing or visualising the GI tract. GIBio provides a mechanism to replicate the dynamic environment of the gut without the costs or variability associated with animal or human studies such that the design, development and manufacture of formulated ingested products will be transformed. GIBio underpins the development of robust products by providing clinical quality data early in development to accelerate the translation of healthcare technologies to patients. This gold standard equipment, the only accessible facility in the UK, will reduce the time and costs associated with the design, development and manufacture of new drug products. Oral administration is the most common drug delivery route. Absorption of a drug from the gut into the bloodstream involves disintegration of the dosage form, dissolution of the drug, and transport across the gut wall. The efficiency of these processes is determined by highly complex and dynamic interactions between the gastrointestinal tract, the dosage form and the drug. This complex interplay determines drug delivery performance and may cause large interindividual variability, but is poorly understood. The fine tuning of the equipment to reproduce the gut in health and disease will ensure that patient centric products are developed to improve therapeutic outcomes. Furthermore, GIBio will generate new research opportunities in formulated ingested products from the food, including animal feed industries and in the evaluation of ingested sensors and medical devices.

Lay abstract: GIBio brings together state of the art engineered models of the stomach as an advanced gastric compartment (TIMagc); a small intestinal modular unit (TIM-1) and a colon unit (TIM-2). Flexibility exists to operate the system to replicate healthy and diseased adult gastro-intestinal (GI) conditions as well as paediatrics and certain animal species within the operating interface. Output data from GIBio has been linked to in vivo data from humans such that the data generated is considered to be "near clinical", thus negating the need for animal and human studies at this early stage in product development. Specifically, access to GIBio enables early understanding of in vivo product performance such that product design and manufacture can be optimised earlier in the development timeline. The research enabled will: (i) Provide early feedback on ingested products by linking product critical quality attributes to in vivo performance to deliver a step change in our understanding of how the dynamic conditions in the GI tract dictate product performance. (ii) Understand the extremes of GI variability and how these influence in vivo performance, in turn, this will permit the development of novel dosage forms that account for GI variability such that patient centric products are produced (iii) Provide relevant input data to develop a digital twin of the GI tract that mimics drug dissolution and absorption To ensure the impact of this project is fully realised we have partnered with key stakeholders in UK academia and pharmaceutical industry.

Research activity codes: 5.1 PHARMACEUTICALS;5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: ORAL AND GASTROINTESTINAL