Abstract
This collection of contributions from the European Network on Understanding Gastrointestinal Absorption-related Processes (UNGAP) community assembly aims to provide information on some of the current and newer methods employed to study the behaviour of medicines. It is the product of interactions in the immediate pre-Covid period when UNGAP members were able to meet and set up workshops and to discuss progress across the disciplines. UNGAP activities are divided into work packages that cover special treatment populations, absorption processes in different regions of the gut, the development of advanced formulations and the integration of food and pharmaceutical scientists in the food-drug interface. This involves both new and established technical approaches in which we have attempted to define best practice and highlight areas where further research is needed. Over the last months we have been able to reflect on some of the key innovative approaches which we were tasked with mapping, including theoretical, in silico, in vitro, in vivo and ex vivo, preclinical and clinical approaches. This is the product of some of us in a snapshot of where UNGAP has travelled and what aspects of innovative technologies are important. It is not a comprehensive review of all methods used in research to study drug dissolution and absorption, but provides an ample panorama of current and advanced methods generally and potentially useful in this area. This collection starts from a consideration of advances in a priori approaches: an understanding of the molecular properties of the compound to predict biological characteristics relevant to absorption. The next four sections discuss a major activity in the UNGAP initiative, the pursuit of more representative conditions to study lumenal dissolution of drug formulations developed independently by academic teams. They are important because they illustrate examples of in vitro simulation systems that have begun to provide a useful understanding of formulation behaviour in the upper GI tract for industry. The Leuven team highlights the importance of the physiology of the digestive tract, as they describe the relevance of gastric and intestinal fluids on the behaviour of drugs along the tract. This provides the introduction to microdosing as an early tool to study drug disposition. Microdosing in oncology is starting to use gamma-emitting tracers, which provides a link through SPECT to the next section on nuclear medicine. The last two papers link the modelling approaches used by the pharmaceutical industry, in silico to Pop-PK linking to Darwich and Aarons, who provide discussion on pharmacometric modelling, completing the loop of molecule to man.
Highlights
Since the first development of a treatment for disease, medicines have been administered via the gastrointestinal tract, as the outcome of surgery was often fatal
As evident from the above synopsis, the aspects related to drug interaction with components of the GI fluid and to mucosal permeation capacities of GI drug absorption are tackled only in a few instances with Molecular dynamics (MD) simulations
There, the key part of the model system is treated with a quantum chemical method and the rest is described with a force field
Summary
Since the first development of a treatment for disease, medicines have been administered via the gastrointestinal tract, as the outcome of surgery was often fatal. To predict the effects of in vivo relevant concentrations of bile salts, phospholipids, and fatty acids on these absorption-determining processes during the early stages of drug development, multiple simulated intestinal fluid compositions with different levels of complexity have been introduced (Markopoulos et al, 2015; Fuchs et al, 2015; Vertzoni et al, 2010). For obvious reasons, these biorelevant media are designed to be simple, relatively cheap, and easy to integrate in drug development.
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