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

StomachSim - 一种基于仿生计算机模拟器的研究工具，用于研究药物在胃中的溶解情况

• 批准号: 10041893
• 负责人: Rajat Mittal
• 金额: $ 24.16万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10041893
• 关键词: Address; Adopted; Age; Behavior; Biochemical; Biological Availability; Biomimetics; Cardiovascular system; Complex; Computers; Data; Development; Diabetes Mellitus; Diagnostic; Diffusion; Disease; Dosage Forms; Dose; Drug Delivery Systems; Drug Design; Drug Modelings; Drug usage; Duodenum; Dyspepsia; Environment; Food; Formulation; Gastrointestinal tract structure; Gastroparesis; Health; In Vitro; Lead; Liquid substance; Modeling; Modernization; Musculoskeletal; Obesity; Oral; Patients; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacopoeias; Physiological; Play; Postural adjustments; Process; Research; Respiration; Risk; Role; Route; Stomach; Stomach Content; System; Tablets; Time; absorption; bariatric surgery; base; cell motility; design; drug inhalation; foodborne infection; functional food; gastric secretion substance; gastrointestinal function; high reward; high risk; in silico; in vitro Model; in vivo imaging; insight; motility disorder; novel; nutrition; pill; pressure; sex; simulation; stomach motility; tool; virtual

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.

标题：胃 - 一种基于silico模拟器的仿生型研究工具，用于研究胃中的药物溶解 项目摘要 口头途径是药物管理最常使用的路线，但这也是最复杂的方法 活性药物成分（API）进入身体。这种复杂性是因为药物通过 胃肠道（GI）道不仅取决于与药物及其配方有关的因素，还取决于内容物 摊位和失速运动。当前评估/量化药物溶解的方法取决于 主要的视野模拟器（例如美国药房（USP）设备），但这些模拟器都无法 充分重现运动性混合，剪切和压力的生物含量/仿生条件，也没有 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 模仿患者特异性因素，例如身体疗养，性别，年龄和胃健康。缺乏生物向量 药物溶解的模拟器代表了推进毒品的设计的重大挑战 系统并为个性化口服药物输送系统提供了几乎无法克服的障碍。我们的位置 在胃的仿生模型中，药物溶解和药物释放的模型模型具有潜力 为了克服维特罗模型的许多上述局限性，这些内部研究工具可以 彻底改变了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 高危，高回报的尝试，以证明预测胃中药物溶解的可行性 通过开发“胃口”，由此产生的API生物利用度 胃功能。这项研究将以这种研究工具生成的能力的证明为顶点 关于药物溶解和药物释放的生物含量数据，在该领域的最先进进步。 研究的目的是：（1）证明高级计算流体和质量扩散模型 在现代计算机上使用可以快速，现实地模拟药物溶解和药物释放 在摊位中； （2）证明胃部可以产生生物含量的数据/见解 推进口服药物溶解研究的最先进。这里提出的研究载有几个 技术风险和挑战以及此处采用的研究方法旨在减轻这些风险。