StomachSim - A Biomimetic In-Silico Simulator Based Research Tool for Studying Drug Dissolution in the Stomach

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Title: StomachSim – A Biomimetic In-Silico Simulator Based Research Tool for Studying Drug Dissolution in the Stomach Project Summary The oral route is the one most frequently used for drug administration, but it is also the most complex way for an active pharmaceutical ingredient (API) to enter the body. This complexity is because drug absorption via the gastrointestinal (GI) tract depends not only on factors related to the drug and its formulation, but also the contents of the stomach and stomach motility. The current approach to assessing/quantifying drug dissolution relies primarily on in-vitro simulators such as the US Pharmacopeia (USP) apparatus, but these simulators can neither adequately recreate biorelevant/biomimetic conditions of motility-induced mixing, shear and pressure, nor the biochemical environment associated with food content and gastric secretions. These in-vitro models also cannot mimic patient-specific factors such as body-habitus, sex, age and gastric health. The lack of biorelevant simulators of drug dissolution represents a significant challenge to advancing the design of drugs delivery systems and presents a virtually insurmountable barrier to personalizing oral drug delivery systems. We posit that in-silico models of drug dissolution and drug release in biomimetic models of the stomach have the potential to overcome many of the above-mentioned limitations of in-vitro models and these in-silico research tools could revolutionize our ability to analyze the performance of oral drug delivery systems. The current R21 application is a high-risk, high-reward attempt to demonstrate the feasibility of predicting drug dissolution in the stomach and the resulting API bioavailability via the development of ‘StomachSim’ a novel, biomimetic in-silico simulator of stomach function. The research will culminate with a demonstration of the ability of this research tool to generate biorelevant data on drug dissolution and drug release that significantly advances the state-of-the-art in this arena. The aims of the research are: (1) demonstrate that advanced computational fluids and mass diffusion models employed on modern computers can enable rapid and realistic simulation of drug dissolution and drug release in the stomach; and (2) demonstrate that StomachSim can generate biorelevant data/insights that significantly advance the state-of-the-art in oral drug dissolution research. The research proposed here carries several technological risks and challenges, and the research approach adopted here is designed to mitigate these risks.