Advanced Particle Engineering for Respiratory Drug Delivery Applications

本提案涉及用于呼吸道药物输送的加压定量吸入器领域的技术开发。该领域的技术水平高度发达，但与传统推进剂有关，传统推进剂导致全球变暖，因为它们是非常有效的温室气体。作为回应，该行业伙伴正在准备改用危害较小的替代推进剂。建议的工作将有助于选择一个适当的替代推进剂，并将提供理论基础，预测产品的性能在替代格式。此外，将从理论和实验两方面研究这种切换对基于悬浮液的定量吸入器的稳定性的影响。最后，将设计与新推进剂相容并可用于生物制剂的新微粒类型。这项工作将采用基于对颗粒推进剂相互作用和颗粒形成机制的机械理解的工程方法。目前无法在理论上模拟的影响将在理想化的实验替代系统中进行研究。该行业合作伙伴随后将把研究结果直接纳入正在进行的开发项目，预计这项工作将导致减少此类产品生产和使用过程中的温室气体排放。此外，预计基于悬浮液的定量吸入器平台的适用范围可以扩展到生物制剂，生物制剂在治疗各种呼吸系统疾病（包括哮喘和慢性阻塞性肺病）中显示出巨大的潜力。因此，该项目可能会导致全球环境保护的实质性改善，并为加拿大卫生保健系统带来巨大负担的疾病提供更有效的治疗方法。

This proposal addresses technology development in the area of pressurized metered dose inhalers for respiratory drug delivery. The state of the art in this field is highly developed, but connected to traditional propellants which contribute to global warming because they are very effective greenhouse gases. In response, the industry partner is preparing for a switch to alternative, less harmful propellants. The proposed work will contribute to the selection of an appropriate substitute propellant and will provide the theoretical basis for predictions of product performance in the alternate format. Furthermore, the impact of this switch on the stability of suspension based metered dose inhalers will be studied both theoretically and experimentally. Lastly, new microparticle types that are compatible with the new propellants and can be used for the formulation of biologics will be designed.The work will employ an engineering approach based on mechanistic understanding of particle propellant interactions and particle formation mechanisms. Effects that cannot currently be modeled theoretically will be studies in idealized experimental surrogate systems. The industry partner will then incorporate the results directly into ongoing development projects.It is expected that this work will lead to a reduction in the emission of greenhouse gases during production and use of such products. Furthermore, it is expected that the range of applicability of the suspension based metered dose inhaler platform can be extended to biologics, which have shown great potential in the treatment of a variety of respiratory diseases, including asthma and chronic obstructive pulmonary disease. Hence, this project will likely lead to substantial improvements in environmental protection globally and in more efficacious therapeutics for conditions that place a large burden on the Canadian health care system.