IN SILICO GASTROINTESTINAL SIMULATION MODELS FOR ORAL DRUG ABSORPTION

Abstract

This review outlines the concept of in silico GI simulation models for oral drug absorption. It highlights the gap between standard laboratory testing and actual clinical reality by providing the mechanistic prediction that shows physiological alterations in specific population by using simulation models. As the oral route is the most common route but still prediction of gastrointestinal absorption is a major challenge in drug development because the pH of GIT is different in both gastric environment and in small intestine. Highly acidic gastric environment to alkaline small intestine which can degrade acid labile drug, also there is lack of data on volume and composition of GI fluid in different population. In silico GI simulation models, such as physiologically based pharmacokinetics (PBPK), Advanced compartmental absorption and transit (ACAT), Compartmental Absorption and Transits (CAT), and various software platforms such as Simcyp, GastroPlus, and PK-Sim they provide mechanistic predictions for the oral absorption. These models combine anatomical, physiological, and drug-specific parameter that simulate absorption, distribution, metabolism and elimination processes. They also optimize dosing strategies, guide formulation development, and predict pharmacokinetic variability in different populations. In silico approaches reduce reliance on animal studies, accelerate development, and enhance regulatory decision-making in a oral drug therapy. These types of model can enable Virtual Clinical Trial in future which can replace human testing.