Automated Actuator for Evaluation of Regional Droplet Deposition from Nasal Spray Devices in Nasal Airway Replicas

用于评估鼻喷雾装置在鼻气道复制品中的区域液滴沉积的自动执行器

• 批准号: RTI-2017-00244
• 负责人: Martin, Andrew
• 金额: $ 4.35万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Research Tools and Instruments
• 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=616608
• 关键词: Automated; Actuator; Evaluation; Regional; Droplet

The requested funds will support a new research program to expand our department’s internationally-recognized capabilities in the assessment of pharmaceutical aerosol delivery devices to include testing of devices designed to administer drugs directly to the nasal airways. Nasal drug delivery is widespread in the treatment of allergic rhinitis, a condition affecting approximately 1 in 5 Canadians. Local delivery of corticosteroids to the nasal airways by means of nasal spray pumps is a mainstay in the treatment of rhinitis. In addition, several classes of marketed products have been developed for systemic drug delivery through the nose. Rapid and direct absorption of drug through the nasal epithelium to the systemic circulation enables fast onset of action; fittingly, marketed products in this category include those intended to treat migraine headaches and break-through cancer pain. Finally, intranasal drug delivery has received considerable recent attention as a route of administration through which to bypass the blood-brain-barrier and directly target the brain, thus potentially offering novel treatment options for central nervous system diseases such as Alzheimer’s and Parkinson’s. For all these applications, a critical consideration is the deposition pattern of spray droplets within the nasal airways. Droplets collected in the anterior nasal passages may drip from the nostrils, whereas droplets passing through the nasal cavity to the nasopharynx and larynx miss their site of action, or worse may reach the lungs where adverse side-effects can occur. Despite decades of use, standard mechanical nasal spray pumps suffer inefficiencies in delivery. Competing new devices aim to improve nasal drug delivery through optimization of drug deposition and retention in the nasal airways. Unfortunately, rigorously developed in vitro benchtop methods do not presently exist for predicting in vivo deposition of drugs delivered intranasally. As a result, researchers and developers rely on in vivo studies employing gamma scintigraphy to assess regional and total nasal deposition of radiolabeled drug products. The cost and time requirements associated with conducting in vivo studies preclude their use in the early stages of nasal drug product development, where they would provide invaluable feedback to developers. Accordingly, a clear need exists to develop predictive in vitro test methods through which to provide rapid feedback on anticipated regional deposition patterns, thereby expediting early product development. We are developing test methods incorporating realistic and idealized nasal airway geometries to address this need. The instrumentation to be purchased with the requested funds, namely an automated actuator that permits repeatable and controllable actuation of nasal spray delivery devices, is a critical element to be incorporated into these methods.

申请的资金将用于支持一项新的研究计划，该计划旨在扩大我们部门在评估药物气雾剂输送装置方面的国际公认能力，包括测试设计用于直接将药物输送到鼻腔呼吸道的装置。 鼻腔给药在治疗过敏性鼻炎中很普遍，大约五分之一的加拿大人患有过敏性鼻炎。鼻腔喷雾泵局部给药是治疗鼻炎的主要方法。此外，还开发了几类通过鼻腔全身给药的上市产品。药物通过鼻腔上皮快速而直接地吸收到全身循环中，能够快速起作用；与之相适应，这一类别的市场产品包括那些旨在治疗偏头痛和突破性癌症疼痛的产品。最后，鼻腔给药作为一种绕过血脑屏障直接靶向大脑的给药途径，最近受到了相当大的关注，从而可能为阿尔茨海默氏症和帕金森氏症等中枢神经系统疾病提供新的治疗选择。 对于所有这些应用，一个关键的考虑因素是喷雾液滴在鼻呼吸道内的沉积模式。收集在前鼻道的液滴可能会从鼻孔滴落，而通过鼻腔进入鼻咽和喉部的液滴可能会错过作用部位，或者更糟糕的是，可能会到达肺部，可能会出现不良副作用。尽管使用了几十年，标准的机械鼻喷雾泵在输送过程中效率低下。与之竞争的新设备旨在通过优化药物在鼻呼吸道中的沉积和滞留来改善鼻腔药物的输送。不幸的是，目前还不存在严格开发的体外台式方法来预测鼻腔给药的体内沉积。因此，研究人员和开发人员依靠活体研究，使用伽马闪烁成像来评估放射性标记药物产品的局部和整体鼻部沉积。与进行体内研究相关的成本和时间要求排除了在鼻药产品开发的早期阶段使用它们，因为在那里它们将为开发者提供宝贵的反馈。 因此，显然需要开发预测性的体外测试方法，通过这些方法对预期的区域沉积模式提供快速反馈，从而加快早期产品开发。我们正在开发结合现实和理想化鼻道几何形状的测试方法来满足这一需求。用申请的资金购买的仪器，即允许可重复和可控制地驱动鼻腔喷雾给药装置的自动执行器，是纳入这些方法的关键要素。