The science behind respiratory drug delivery is complex, and consequently there are lots of myths floating around. In this blog series we will dispel five common myths about DPIs. In this, the first blog of the series, we debug the common myth that lower resistance DPIs are “easier to use”.
There is a common misconception that low resistance DPIs are “easier to use”, because the user experiences less resistance when breathing through them, and is consequently able to reach a higher flowrate.
In fact, higher resistance DPIs have better dose consistency between users, with higher Fine Particle Fraction (FPF) and better lung deposition.
The resistance of an inhaler dictates the flowrate through the inhaler, for a given pressure drop. The relationship between device resistance, pressure drop and flowrate is defined as:
Therefore, for a given pressure drop (for example, a pressure drop of 4 kPa is often used in a lab setting), a low resistance DPI will have a higher flowrate of air through it than a high resistance DPI.
Despite the common misconception that low resistance DPIs are “easier to use”, higher resistance DPIs have better dose consistency between users and, if designed correctly, have higher Fine Particle Fraction (FPF) and better lung deposition.
In brief, higher resistance DPIs allow for:
To elaborate further on each point:
All inhaler users will achieve a higher pressure drop across the inhaler when inhaling through a higher resistance DPI (than through a lower resistance device). This is because users achieve their highest inspiratory flowrate under no load (zero resistance); and their highest inspiratory pressure drop under maximum load (infinite resistance). And there is a reasonably linear response between these two extreme scenarios.
Achieving a high-pressure drop is key to creating an efficient aerosolisation engine, and to producing a high fine particle fraction (FPF), because the pressure drop across the device provides the force necessary to create high-velocity airflows through the inhaler, and it is these high velocity airflows that are used to deagglomerate the formulation.
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 inspiratory mouth pressure, which is the maximum pressure drop they can achieve across an infinite resistance device (i.e. zero flow). This is seen in Figure 1 at zero flowrate.
However, the maximum inspiratory capacity (the maximum amount of air a person can inhale after a normal exhalation) will be higher for a healthy adult than a child or COPD patient, because a child’s lungs have not yet reached full size, and some portion of a COPD patient’s lungs no longer functions normally. Data shows that as the inhaler resistance reduces, users with higher usable lung capacity (i.e. healthy adults) can achieve higher inspiratory flowrates, hence the pressure-flow curves (figure 1) of children and adults shown in Figure 1 (for example) diverge.
Figure 1: Effect of age on inspiratory flow characteristics1
Therefore, higher resistance devices will have greater flowrate and pressure drop consistency between users, and therefore more consistent performance and dose, both between patient groups and dose-to-dose.
Therefore, higher resistance devices will have greater flowrate and pressure drop consistency between users, and therefore more consistent performance and dose, both between patient groups and dose-to-dose.
As users achieve lower flowrates through higher-resistance inhalers, it takes more time to fill their lungs and so the duration of inhalation is increased, which lengthen the time over which deagglomeration work can be done on the powder.
As the patients inhale with lower flowrates through a higher resistance inhaler, the air velocities through their oropharynx, upper airways and bronchioles within the lungs will be lower. These lower airflow velocities are less likely to cause inertial impaction of respirable particles, which results in an aerosol of a given particle size distribution penetrating deeper into the lungs, and a greater overall therapeutic effect.2
Whilst it is true that some patients report a preference for lower resistance devices, because they may find the high resistance uncomfortable to inhale through, this should not be mistaken for ease of use if it does not relate to therapeutic effect. Instead, if ease of use relates to how easy it is for different patient groups to achieve the same therapeutic dose, then higher resistance devices should in fact be easier to use.