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

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.