Comprehensive Experimental and Numerical Studies of Pharmaceutical Aerosol Devices

药用气雾剂装置的综合实验和数值研究

• 批准号: RGPIN-2016-06239
• 负责人: Matida, Edgar
• 金额: $ 1.89万
• 依托单位: Carleton University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=710226
• 关键词: Comprehensive; Experimental; Numerical; Studies; Pharmaceutical

Pressurized metered-dose inhalers (pMDIs) or “puffers”, dry powder inhalers (DPIs), and nebulizers are normally used in the treatment of lung diseases, such as asthma and bronchitis. Statistics from Lung Associations indicate that up to approximately 10% of the population may suffer from respiratory illnesses requiring treatment in part of their lives. Inhaler devices produce very complex turbulent flows and ideal medication delivery remains a challenging engineering problem. Considerable amounts of aerosol medication generated from the pMDIs are deposited and lost on the walls of the upper airways (mouth-throat-trachea) before reaching the target (or the lungs), resulting in considerable medication losses from a single dosage (Fink, 2000). Add-on spacers (normally cylindrical chambers) are devices that are attached to the pMDIs and will enhance the total amount of medication delivered to the lungs. Besides medication delivery to the lungs, nasal drug delivery using pharmaceutical aerosols is emerging as an important alternative for treating many conditions such as diabetes (insulin delivery), osteoporosis, and even migraine headaches. Due to complexity of the nasal cavity and differences in regional medication absorptiveness, which is also affected by the medication properties (formulation and aerosol size distribution characteristics) and fluid flow structures, the ideal nasal drug delivery remains a challenging problem. In collaboration with the Ottawa Civic Hospital, we have been developing a novel and idealized nasal cavity geometry, which is a potential candidate to be used as a standard (for aerosol deposition measurements) in the pharmaceutical field. Despite the importance and growing interest in inhaled medications, research and development of pharmaceutical aerosol devices have focused more on therapeutical effectiveness. More efficient inhalation devices will reduce side effects (like muscle cramps and sore throat) and improve patients' compliance, thus reducing duration and costs of treatment. The present proposed research aims at the better understanding of the physics involved in aerosol drug delivery systems (both lung and nasal) and the improvement of the performance of inhalation devices in terms of maximizing medication delivery, through ongoing comprehensive studies of aerosol generation, transport, and deposition inside devices themselves and mainly in extra-thoracic airways (nose-mouth-throat), using experimental analysis (aerosol deposition and fluid flow measurements) and Computational Fluid Dynamics (CFD). The author also wishes to use similar approaches and expand the investigations towards the understanding (transport and extra-thoracic deposition mechanisms) and characterization of airborne allergic triggers with a focus on PM2.5 (particulate matter with diameter smaller than 2.5 microns), especially nanoparticles.

加压计量吸入器(PMDI)或“喷雾器”、干粉吸入器(DPI)和雾化器通常用于治疗哮喘和支气管炎等肺部疾病。肺脏协会的统计数据表明，多达10%的人口可能患有呼吸系统疾病，需要在他们生命的一部分进行治疗。吸入器装置会产生非常复杂的湍流，理想的药物输送仍然是一个具有挑战性的工程问题。从pMDIs产生的相当数量的气雾剂药物在到达目标(或肺部)之前沉积并丢失在上呼吸道(口-喉-气管)的壁上，导致单次剂量的药物损失相当大(Fink，2000)。附加间隔物(通常为圆柱形腔室)是连接到PMDI上的设备，将增加向肺部输送的药物总量。 除了肺部的药物输送，使用药物气雾剂的鼻腔给药正在成为治疗糖尿病(胰岛素输送)、骨质疏松症甚至偏头痛等多种疾病的重要替代方案。由于鼻腔的复杂性和不同区域药物吸收能力的差异，以及药物性质(制剂和气雾剂的粒度分布特征)和流体流动结构的影响，理想的鼻腔给药仍然是一个具有挑战性的问题。与渥太华市政医院合作，我们一直在开发一种新颖的、理想化的鼻腔几何结构，这是一种潜在的候选方案，可用作制药领域的标准(用于气溶胶沉积测量)。 尽管吸入性药物的重要性和日益增长的兴趣，但药物气雾剂设备的研究和开发更多地集中在治疗效果上。更有效的吸入设备将减少副作用(如肌肉痉挛和喉咙痛)，并提高患者的依从性，从而缩短治疗时间和降低治疗成本。目前拟议的研究旨在通过使用实验分析(气溶胶沉积和流体流动测量)和计算流体动力学(CFD)对气雾剂在装置内部和主要在胸外呼吸道(鼻-口-喉部)内的产生、传输和沉积进行持续的全面研究，以更好地了解气雾剂给药系统(包括肺部和鼻腔)所涉及的物理学，并在最大限度地给药方面改善吸入装置的性能。作者还希望使用类似的方法，扩大对空气传播过敏诱因的理解(运输和胸外沉积机制)和特征的研究，重点是PM2.5(直径小于2.5微米的颗粒物)，特别是纳米颗粒。