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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=616180
• 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“吹气器”、干粉吸入器 (DPI) 和雾化器通常用于治疗肺部疾病，例如哮喘和支气管炎。肺脏协会的统计数据表明，高达约 10% 的患者会使用这种吸入器。人们在生活中可能会患有呼吸系统疾病，需要接受治疗。吸入器会产生非常复杂的湍流，而理想的药物输送仍然是一个具有挑战性的工程问题。 PMDI 产生的气溶胶药物在到达目标（或肺部）之前会沉积并损失在上呼吸道（口-咽-气管）壁上，导致单剂量药物损失相当大（Fink，2000）。隔离器（通常为圆柱形腔室）是连接到 pMDI 的装置，可增加输送到肺部的药物总量。 除了向肺部输送药物外，由于鼻腔的复杂性和区域药物的差异，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许多疾病的重要替代方案。吸收性也受到药物特性（配方和气雾剂尺寸分布特征）和流体流动结构的影响，理想的鼻腔药物输送仍然是一个具有挑战性的问题，我们与渥太华市民医院合作，一直在开发一种新颖的药物。理想化的鼻腔几何形状，是制药领域用作标准（气溶胶沉积测量）的潜在候选者。 尽管吸入药物的重要性和兴趣日益浓厚，但药物气雾剂装置的研究和开发更多地关注治疗效果，更有效的吸入装置将减少副作用（如肌肉痉挛和喉咙痛）并提高患者的依从性，从而缩短持续时间和时间。目前提出的研究旨在通过持续进行的气雾剂综合研究，更好地了解气雾剂药物输送系统（肺和鼻）所涉及的物理原理，并提高吸入装置在最大化药物输送方面的性能。作者还希望使用类似的方法，利用实验分析（气溶胶沉积和流体流量测量）和计算流体动力学（CFD），在设备本身内部，主要是在胸外气道（鼻-口-喉）中产生、运输和沉积。方法并扩大研究范围，以了解（传输和胸腔外沉积机制）和空气中过敏触发因素的特征，重点关注 PM2.5（直径小于 2.5 微米的颗粒物），特别是纳米颗粒。