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The science

We love to get nerdy about the science that underpins all of our inhaler platform technologies.
This page gives an introduction, but if you’re interested to know more, please get in touch – we’re always happy to talk details!

 

 

"The perfect respiratory drug delivery system would deliver a known quantity of drug to the required part of the lung, completely independently of how the patient inhales, and avoid any unpleasant side-effects caused by deposition of API in the mouth and throat."
David HarrisCo-founder & CEO of CHI

The perfect inhaler. That's our goal.

Delivering drugs to the lung

The role of a respiratory drug delivery system is to break up the formulation into respirable particles (or droplets) and entrain them into the patient's inhalatory airflow.

The fraction of the formulation which is broken up into respirable-sized particles (typically less than 5 μm aerodynamic diameter) is known as the Fine Particle Fraction (FPF). Increasing the FPF increases the proportion of the dose which reaches the lungs, thereby increasing the effective dose and reducing drug wastage and cost.

Achieving a consistent FPF across users is essential for reliable dosing. Unfortunately, because respiratory devices rely on the patient inhaling the dose, there is an inherent user dependence for all device types.

How do traditional DPIs work?

The powder within a Dry Powder Inhaler (DPI) is typically formed of tiny respirable particles of the drug itself (the Active Pharmaceutical Ingredient, or API) attached to larger, inactive ‘carrier’ particles, usually lactose. 

When the patient inhales, some of the inspiratory energy is harnessed to move the powder through the inhaler. This causes a portion of the API to become detached from the lactose particles ("deagglomerated") and make it to the lung. For most DPIs, this portion – the FPF – is typically only 20-40% of the API. The rest of the API stays attached to the large lactose particles and lands in the mouth and throat, which can cause unpleasant side effects.

In recent years API-only formulations, without carrier fraction, have grown in prevalence. Clumps (agglomerates) of the powder are broken up (deagglomerated) into fine particles as they move through the inhaler.

Energy source

In a DPI, energy is needed to deagglomerate and aerosolise the powder. In a passive DPI this energy comes solely from the patient's own inhalation effort. 

The more energy that is transferred into the powder, the higher the Fine Particle Fraction (FPF) will be.

Because the energy is provided by the patient's inhalation effort, the total amount of energy available will vary from patient to patient (for example, depending on lung capacity). However, the proportion of the energy that is transferred to the powder will depend on the inhaler design.

Surprisingly, most existing DPIs only transfer a tiny portion of the total available energy from the inhalation effort into the powder.

The energy curve for a DPI

Figure 1 schematically illustrates how increasing the amount of energy which is transferred into the powder in a DPI increases the Fine Particle Fraction (FPF) of the delivered dose.

Importantly, the FPF does not increase linearly with increasing input energy. Consequently, the performance curve can be considered in two parts — a steep part (Zone 1) and a flatter part (Zone 2).

 

Brand colour graph more captions 03
Figure 1: Illustrative schematic of the effect of energy transferred to the powder on fine particle fraction (FPF). Hover over the purple dots for more insights.

Most existing DPIs operate in Zone 1, where a small change in user inhalation effort (energy) has a big impact on FPF. This results in:

  • High dose-to-dose variability
  • Dose is highly user dependent
  • Failure to achieve market approval due to excessive dosing variability  

 

The reason for this is not due to a shortage of inhalation energy, but because existing DPIs actually waste most of the available energy.

A DPI operating in Zone 2 would have both better performance (higher FPF) and better consistency. The good news is that the total energy needed to reach Zone 2 is a fraction of the energy that even someone with poor lung function can provide.

 

The challenge is not the amount of energy available, but making effective use of it

 

A platform for your formulation

Our three inhaler platforms Quattrii, Aeolus and Occorix, each transform the available input energy to optimise for the specific formulation and fill mass to maximise the fraction of the available energy which is transferred to the powder. Therefore, maximising Fine Particle Fraction and dose consistency and minimising mouth and throat deposition.

Learn more about each of our platforms: