Advanced Particle Engineering for Respiratory Drug Delivery Applications

本提案涉及用于呼吸输送药物的加压计量吸入器领域的技术发展。这一领域的技术水平是高度发达的，但与传统的推进剂有关，因为它们是非常有效的温室气体，会导致全球变暖。作为回应，该行业合作伙伴正准备改用危害较小的替代推进剂。拟议的工作将有助于选择适当的替代推进剂，并将为预测替代格式下的产品性能提供理论基础。此外，该开关对悬浮液计量吸入器稳定性的影响将从理论和实验两方面进行研究。最后，将设计与新型推进剂兼容并可用于生物制剂配方的新型微粒类型。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效应将在理想化的实验替代系统中进行研究。然后，行业合作伙伴将直接将结果合并到正在进行的开发项目中。预计这项工作将导致在这些产品的生产和使用过程中减少温室气体的排放。此外，预计基于悬浮液的计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）方面显示出巨大潜力。因此，该项目可能会导致全球环境保护的实质性改善，并为加拿大医疗保健系统带来更有效的治疗方法。

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.