10 www.ondrugdelivery.com Copyright © 2015 Frederick Furness Publishing Ltd Team Consulting David Harris Head of Respiratory Drug Delivery T: +44 1799 532 767 E: david.harris@team-consulting.com Team Consulting Ltd Abbey Barns Duxford Road Ickleton Cambridge CB10 1SX United Kingdom www.team-consulting.com WHY IS HIGH RESISTANCE GOOD FROM A PATIENT’S PERSPECTIVE? A question dry-powder inhaler (DPI) device developers always face is: “What airflow resistance should I make the device?” Many studies have been conducted and the results often published, but there still appears to be no commonly agreed answer about what is best. The airflow resistance of the pressurised metered dose inhaler (pMDI) is rather arbitrary, as pMDIs produce a respirable aerosol completely independently of how the user inhales. DPIs, on the other hand, rely solely upon the energy available in the user’s inspiratory manoeuvre – some of which is transferred into the bulk powder to transform it into a respirable aerosol. There are several performance factors that are directly affected by the resistance of a DPI… 1. Pressure Drop All inhaler users will achieve a higher pres- sure drop across the device when inhaling through a higher-resistance DPI. This is because users achieve their highest inspira- tory flowrate under no load (zero resist- ance); and their highest inspiratory pres- sure drop under maximum load (infinite resistance). And there is a reasonably linear response between these two extreme sce- narios. Achieving a high pressure drop is key to creating an efficient aerosolisation engine, and to producing a high fine par- ticle fraction (FPF), as it is the inspiratory pressure drop that provides the force neces- sary to create high-velocity airflows within the inhaler. 2. Consistency The lungs of children and COPD patients are powered by muscles that are more or less as strong as a healthy adult’s. This means that, on average, all three patient groups converge toward a common peak maximal inspira- tory mouth pressure, which is the maxi- mum pressure drop they can achieve across an infinite resistance device (i.e. zero flow). However, their maximal inspiratory capacity is significantly less than a healthy adult’s; a child’s because their lungs are not yet fully grown, and a COPD patient’s because some proportion of their lungs no longer function normally. Data shows that as the device resist- ance decreases, users with higher usable lung capacity can achieve higher inspiratory flow- rates, and the pressure flow curves of children and adults (for example) diverge (Figure 1). 1 3. Duration of Inhalation As users achieve lower flowrates through higher-resistance inhalers, it takes more time to fill their lungs and so the duration of inha- lation is increased. 4. Lung Deposition The air velocities within their oropharynx, upper airways and bronchioles within the lungs will be lower when inhaling through a high-resistance device due to the limited maximum inspiratory flowrate that can be achieved. These lower airflow velocities are less likely to cause inertial impaction of res- pirable particles, which results in an aerosol of a given particle size distribution penetrat- ing deeper into the lungs, and a greater over- all therapeutic effect. 2 In this article, David Harris, Head of Respiratory Drug Delivery, Team Consulting, taps into a powerful combination of detailed anatomical and functional understanding of the human respiratory system, pulmonary drug delivery technology and formulation expertise, and mathematical modelling techniques, in order to put forward the case for high-resistance swirl chambers in dry-powder inhalers, and a rational strategy for optimising the design and thus maximising therapeutic efficacy. THE ADVANTAGES OF DESIGNING HIGH-RESISTANCE SWIRL CHAMBERS FOR USE IN DRY-POWDER INHALERS