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

StomachSim--一种基于仿生In-Silico模拟器的研究工具，用于研究药物在胃中的溶出 项目摘要 口服给药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(原料药)进入人体。这种复杂性是因为药物通过 胃肠道不仅取决于与药物及其制剂有关的因素，而且还取决于药物的含量。 对胃和胃运动的影响。目前评估/量化药物溶出度的方法依赖于 主要是体外模拟器，如美国药典(USP)仪器，但这些模拟器既不能 充分重建运动诱导的混合、剪切和压力的生物悬浮/仿生条件，也不 与食物含量和胃分泌物相关的生化环境。这些体外模型也不能 模仿患者特定的因素，如身体习惯、性别、年龄和胃健康。生物悬浮剂的缺乏 药物溶出度模拟器是推进药物输送设计的重大挑战 这对个性化口服给药系统构成了一个几乎不可逾越的障碍。我们假设 在胃的仿生模型中，药物释放和药物释放的电子计算机模型具有潜在的 为了克服体外模型和这些硅胶研究工具的许多上述限制， 彻底改变了我们分析口服给药系统性能的能力。当前的R21应用程序是 一项高风险、高回报的尝试，旨在证明预测药物在胃和胃中溶出的可行性 通过开发一种新型的仿生硅内模拟器StomachSim来实现原料药的生物利用度 胃功能。这项研究将以展示这一研究工具产生 关于药物溶解和药物释放的生物悬浮数据，显著推进了这一领域的最新技术。 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 以及(2)证明StomachSim可以产生显著的生物悬浮数据/见解 推进口服药物溶出度研究的最新进展。这里提出的研究包含了几个 技术风险和挑战，而这里采用的研究方法就是为了缓解这些风险。

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.