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Modeling Complex Particle Interactions in Dry Powder Inhaler Based Drug Delivery

干粉吸入器药物输送中复杂颗粒相互作用的建模

基本信息

批准号：
10709061
负责人：
Sankaran Sundaresan
金额：
$ 1.18万
依托单位：
PRINCETON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10709061
关键词：
Modeling Complex Particle Interactions Dry

项目摘要

Project Abstract Title: Modeling complex particle interactions in dry powder inhaler based drug delivery. Abstract: Dry powder inhalers (DPIs) are used to deliver drugs directly to human airways and lungs, and are often used to treat medical conditions such as asthma or emphysema. The active drug particles used in DPIs are often very small, typically less than 5 micrometers. The small size makes them very cohesive, which reduces their flowability. Large carrier particles that aggregate with the smaller drug particles are employed to facilitate drug delivery. The agglomeration and deagglomeration processes that are central to DPI drug delivery are affected by a variety of factors including inter-particle cohesion due to van der Waals interaction, Coulombic and dielectrophoretic forces between charged particles and turbulence in the inhaler and human airways. Accurate modeling of fluid flow and particle motion, accounting for all these forces, is vital for thorough understanding of drug delivery using DPIs. Coulombic forces between charged particles have been widely studied in the particle technology literature; however, dielectrophoresis, which has been shown to play an essential role in clustering of seemingly identical dielectric particles, has received much less attention. As the drug and carrier particles used in DPI are usually dielectric materials, dielectrophoresis is very likely to play a significant role in agglomeration in DPIs. Including this force in DPI analysis for the first time in the literature would be a novel aspect of the proposed work. The main challenge in modeling electrostatic forces between particles lies in determining the particle charge that originates from contact charging between the particles and the device internals. Prior DPI studies have simply specified the charges on the particles, which are usually not known. The most widely used approach in literature to model the extent of particle charging via contact charging employs effective work function of each material as a phenomenological parameter to characterize charge transfer between two contacting surfaces. This approach has been employed in the research group of the PIs to study the interplay of gas-particle fluidization and particle charging; the proposed research would introduce this approach to DPI studies for the first time in the literature. In this proposal, we will develop a CFD-DEM simulation tool based on open-source platforms. Emphasis will be based on implementing models for all the known physics, including van der Waals force, fluid turbulence, Coulombic and dielectrophoretic forces and contact charging. The code will be validated against experimental data from the literature and also used to perform simulations exploring the importance of various physical characteristics of the particles.

项目摘要标题：模拟基于干粉吸入器的药物递送中的复杂颗粒相互作用。翻译后摘要：干粉吸入器（DPI）用于将药物直接输送到人体气道，肺，并经常用于治疗医学疾病，如哮喘或肺气肿。活性 DPI中使用的药物颗粒通常非常小，通常小于5微米。小尺寸使它们非常粘聚，这降低了它们的流动性。大的载体颗粒，使用具有较小药物颗粒的聚集体来促进药物递送。对DPI药物递送至关重要的聚集和解聚集过程是受到多种因素的影响，包括由于货车德瓦尔斯相互作用而引起的颗粒间凝聚力，吸入器中带电粒子与湍流之间的库仑力和介电泳力和人体呼吸道流体流动和颗粒运动的精确建模，力，是至关重要的药物输送使用DPI的透彻理解。库仑力在粒子技术文献中已经广泛地研究了带电粒子之间的相互作用; 然而，介电电泳，这已被证明发挥重要作用，在集群的看似相同的电介质颗粒，受到的关注要少得多。作为药物和载体 DPI中使用的颗粒通常是介电材料，介电电泳很有可能起到介电作用。在DPIs的聚集中起重要作用。年首次将这支部队纳入新闻部的分析，文献将是拟议工作的一个新方面。模拟粒子间静电力的主要挑战在于确定源自粒子与器件之间接触充电的粒子电荷内部以前的DPI研究只是简单地指定了粒子上的电荷，这些电荷通常是不知道。在文献中最广泛使用的方法来模拟粒子充电的程度通孔接触充电采用每种材料的有效功函数作为现象学的参数来表征两个接触表面之间的电荷转移。这种方法有曾在PI研究组中研究气粒流化的相互作用和粒子充电;拟议的研究将把这种方法引入DPI研究，这是文学史上的第一次。在这个方案中，我们将开发一个基于开源平台的CFD-DEM模拟工具。重点将基于所有已知的物理模型的实现，包括货车德尔瓦尔斯力，流体湍流，库仑力和介电泳力和接触充电。的代码将根据文献中的实验数据进行验证，并用于执行模拟探索粒子的各种物理特性的重要性。