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

标题：StomachSim -一种基于仿生硅模拟器的研究工具，用于研究药物在胃中的溶解 项目摘要 口服途径是最常用的给药途径，但也是最复杂的给药途径。 活性药物成分（API）进入体内。这种复杂性是因为药物通过 胃肠道（GI）不仅取决于与药物及其制剂相关的因素，还取决于药物的内容物 胃和胃的运动。目前评估/量化药物溶出度的方法依赖于 主要是在体外模拟器如美国药典（USP）装置上，但这些模拟器既不能 充分重建运动诱导的混合、剪切和压力的生物相关/仿生条件， 与食物内容物和胃分泌物相关的生化环境。这些体外模型也不能 模拟患者特定因素，如体型、性别、年龄和胃健康。缺乏生物相关性 药物溶出模拟器是推进药物输送设计的一个重大挑战 系统，并提出了一个几乎不可逾越的障碍，个性化的口服药物输送系统。我们断定 药物溶解和药物释放的计算机模拟模型在胃的仿生模型中具有潜力， 为了克服上述体外模型的许多局限性，这些计算机研究工具可以 彻底改变我们分析口服药物输送系统性能的能力。当前的R21应用程序是 一个高风险，高回报的尝试，以证明预测药物在胃中溶解的可行性， 通过开发“胃Sim”（一种新型的仿生计算机模拟器）， 胃功能这项研究将达到高潮，演示这种研究工具的能力，以产生 关于药物溶解和药物释放的生物相关数据，其显著地推进了该竞技场的最新技术水平。 研究的目的是：（1）证明先进的计算流体和质量扩散模型 在现代计算机上使用，可以快速和逼真地模拟药物溶解和药物释放 （2）证明StomachSim可以生成生物相关数据/见解， 推进口服药物溶出度研究的最新发展。这里提出的研究进行了几个 技术风险和挑战，这里采用的研究方法旨在减轻这些风险。

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.