Investigation of fluidization and aerosolisation behavior of dry powder inhalers, with the aim of improving control of particle size

干粉吸入器是将药物输送到肺部的常用设备。它们最常用于治疗慢性气道疾病，如哮喘和COPD，但偶尔也用于将治疗剂输送到体循环中。为了成功地吸入气道的较深部分，干粉必须流化和雾化。颗粒的形状，特别是大小是决定吸入粉末到达深度的关键。反过来，深度又会影响活性成分是主要在肺部起作用，还是被全身吸收。了解这一点对治疗的效果和潜在的副作用都很重要。如果颗粒太大或没有正确分散，它们可能会进入喉咙；如果它们的直径大于10微米，这是可能的。非常细的颗粒，可能小于3微米，可以到达末端细支气管和肺泡。这些气囊的大表面积会导致到达它们的药物被全身吸收。直径也会影响颗粒的“粘性”，这将对粉末雾化的难易程度产生影响。颗粒的大小也决定了吸入颗粒进入肺部或被呼出从而从气道排出的倾向。该项目的目的是利用我们对当前干粉吸入器系统的流化和分散行为的理解，以及这些设备内可用的能量。该项目将结合粉末科学、装置设计和流体动力学。这些研究结果将用于确定其他能源，能够有效地雾化大量和少量粉末的干粉配方。这项研究具有重要的未来效益。干粉吸入器的替代品是含有气溶胶推进剂的加压计量吸入器（pmdi）。这种推进剂曾经含有氯氟烃，但由于众所周知的对臭氧层的有害影响，这种气体的使用最终被禁止。这意味着许多pmdi必须使用替代的非氯氟烃气体重新配制。不幸的是，这意味着一些重要的药物无法以pMDI的形式获得，因为它们无法重新配制。新型pMDI推进剂“HFAs”也会破坏环境，因为它们是强大的温室气体。这些pMDI问题导致了对干粉吸入器的新需求，因此这项研究处于吸入器设计的前沿。该项目由工程和物理科学研究委员会部分资助。它将涉及工程，因为可能需要开发新的吸入器装置。特别地，我们可以看看“活性”干粉吸入器，其中外部能量被添加到设备中，以使其准备使用。粉末流动和分散的研究是物理化学的一项练习。粉末分散的物理尚未完全理解，本研究可能阐明这一基础科学在一个应用的设置。总之，本项目的目的是研究干粉吸入器系统的粉末流动和分散行为。必须控制颗粒大小和形状，因为这将决定治疗剂的深度和范围。将粉末分散成细颗粒气溶胶尤为重要，但这需要能量。本研究将研究装置的设计和配方，以提高粉末雾化的效率和效果。

Dry powder inhalers are popular devices for delivering drugs to the lungs. They are most often used to treat chronic airway diseases such as asthma and COPD but have occasionally been used to deliver therapeutic agents into the systemic circulation. To be successfully inhaled into the deeper parts of the airways the dry powder must be fluidized and aerosolized. The particle shape and especially size are crucial in determining the depth the inhaled powder reaches. The depth, in turn, affects whether the active ingredient will act primarily in the lung or whether it will be systemically absorbed. Understanding this is important both for the efficacy of therapy and potential side-effects. If particles are too large or not properly dispersed they may lodge in the throat; this is likely if their diameter is greater than 10 microns. Very fine particles, perhaps less than 3 microns can reach the terminal bronchioles and alveoli. The large surface area of these air sacs can lead to the systemic absorption of drugs that reach them. Diameter also influences how 'sticky' particles are and this will have a bearing on the ease with which the powder will aerosolize. Size also determines the propensity of inhaled particles to lodge in the lung or to be exhaled and thus expelled from the airways.The aim of this project is to utilize our understanding of the fluidization and dispersion behavior of current dry powder inhaler systems with the energy available within these devices. The project will interface between powder science, device design and fluid dynamics. These research findings will be used to identify other energy sources capable of efficiently aerosolizing dry powder formulations for both large and small amounts of powder. This research has important future benefits. The alternative to dry powder inhalers are pressurized metered dose inhalers (pMDIs) which contain an aerosol propellant. This propellant used to contain CFCs but the use of such gases was eventually prohibited due to their well-known harmful effects on the ozone layer. This meant that many pMDIs had to be reformulated using an alternative, non-CFC gas. This meant, unfortunately, that some important drugs became unavailable in pMDI form as they could not be reformulated. The new pMDI propellants, 'HFAs' are also environmentally damaging as they are powerful greenhouse gases. These pMDI problems have led to a renewed demand for dry powder inhalers and so this research is well-positioned at the cutting edge of inhaler design. This project is part-funded by the Engineering and Physical Sciences Research Council. It will involve engineering as new inhaler devices may need to be developed. In particular we may look at 'active' dry powder inhalers, where external energy is added to the device in order to prime it for use. The study of powder flow and dispersion is an exercise in physical chemistry. The physics of powder dispersion are not fully understood and this research may elucidate this underlying science in an applied setting.In summary the purpose of this project is to investigate the powder flow and dispersion behavior of dry powder inhaler systems. Particle size and shape must be controlled as this will determine the depth and extent of the therapeutic agent. It is especially important to disperse the powder into a fine particle aerosol but this requires energy. The research will study device design and formulation to improve the efficiency and effectiveness of powder aerosolization.