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

干粉吸入器是一种流行的向肺部输送药物的设备。它们最常用于治疗哮喘和慢性阻塞性肺病等慢性呼吸道疾病，但偶尔也被用来将治疗剂输送到体循环中。为了成功地将干粉吸入呼吸道的更深部位，必须使干粉流态化和雾化。颗粒的形状，特别是大小，是决定吸入粉末到达深度的关键。深度反过来又会影响活性成分是否主要在肺部起作用，或者是否会被全身吸收。了解这一点对于治疗的有效性和潜在的副作用都很重要。如果颗粒太大或没有适当分散，它们可能会滞留在喉咙里；如果它们的直径大于10微米，就有可能发生这种情况。非常细的颗粒，可能不到3微米，可以到达终末细支气管和肺泡。这些气囊的大表面积可以导致到达它们的药物的全身吸收。直径也会影响颗粒的“粘性”程度，这将影响粉末的雾化程度。大小还决定了吸入颗粒物进入肺部或被呼出并从呼吸道排出的倾向。本项目的目的是利用这些设备中可用的能量来利用我们对当前干粉吸入器系统的流态化和分散行为的理解。该项目将把粉末科学、设备设计和流体力学结合起来。这些研究成果将被用来确定能够有效地雾化大小粉末的干粉配方的其他能源。这项研究对未来有重要的好处。干粉吸入器的替代品是含有气雾剂推进剂的加压计量吸入器(Pmdi)。这种推进剂过去含有氯氟化碳，但由于其对臭氧层的众所周知的有害影响，最终禁止使用这种气体。这意味着许多私营计量吸入器必须改用替代的、不含氟氯化碳的气体。不幸的是，这意味着一些重要的药物不能以pMDI的形式提供，因为它们不能重新配制。新的pMDI推进剂‘HFA’也对环境造成破坏，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一轮需求，因此这项研究处于吸入器设计的前沿。这个项目由工程和物理科学研究理事会提供部分资金。这将涉及工程，因为可能需要开发新的吸入器设备。特别是，我们可能会考虑“主动”干粉吸入器，即在设备中添加外部能量，以便为其使用做好准备。粉末流动和分散的研究是物理化学中的一项练习。粉末分散的物理原理还不完全清楚，这项研究可能会在应用环境中阐明这一基本科学。总而言之，本项目的目的是调查干粉吸入器系统的粉末流动和分散行为。必须控制颗粒的大小和形状，因为这将决定治疗剂的深度和范围。特别重要的是将粉末分散成细小的气雾剂，但这需要能量。这项研究将研究设备设计和配方，以提高粉末气雾化的效率和效果。

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.