Inhaled drug therapy has become a preferred administration route for many respiratory drugs, by targeting delivery to the lungs, relatively small amounts of medication can produce a marked clinical response. When drug therapy is inhaled, the drug is not distributed throughout the body (as happens with medication that is administered by tablet, skin-patch or injection); so the amount of drug needed is therefore small, and as a consequence, the risk of side effects is reduced.
Speed of inhalation has been found to be important for two major reasons:-
1) How the aerosol cloud travels to the lungs
2) How efficient the inhaler system is in producing the aerosol
1) How the aerosol cloud travels to the lungs
To eventually reach the target site, the small dose of drug released from an inhaler must travel through the mouth to the oropharynx, and then follow the airway down to the bronchi and then on to the lungs. Ideally, all of the drug contained in the aerosol would reach the intended site, but even in the best cases, much of the dose never reaches it.
There are several reasons for this, but two important influences are
a) Aerosol particle size
b) Airway geometry
Aerosol particle size
To achieve maximum effect, medication needs to pass through the large airways to reach the smaller airways deeper within the lung. If the aerosol particles are too large in diameter (above 6 microns), they are deposited in the oropharynx and mouth, but for smaller particles (between 2 and 6 microns), they can reach the smaller airways where they have their effect.
Most aerosols are made up of particles of a range of sizes if the majority of the particles are small, then more of the drug will reach the target site.
Airway geometry
The route the aerosol cloud must follow to reach the lungs is made up of a series of bends and branches (called bifurcations), where the main airway splits into two or more smaller air passageways. These bifurcations happen many times before the airways eventually end, at the alveoli. The medication particles must be carried in the airflow without impaction on the large airway walls the more that do impact; the less dose is carried to the smaller airways.
How Aerosols travel to the Target Site
Together, particle size, airway geometry and speed of inhalation determine the quantity of aerosol that is deposited; the physics of aerosol deposition is a complex science, but simplified, it can be explained that
a) Large particles are more likely than small particles to impact on a bend or bifurcation in airway, and
b) Particles travelling fast are more likely to impact on the route through the lungs, compared to particles travelling slowly
The conclusion is that a slower inhalation is better than a fast inhalation, and small particles result in better lung deposition than large particles.
2) How efficient the inhaler system is
By comparison to the benefit that slower inhalation has on passage of an aerosol within the lung as explained above, some inhalers operate efficiently only when air is drawn through them quickly. The class of inhaler they belong to (called Dry Powder Inhalers or DPIs) rely on the airflow through the device to create the aerosol cloud generally, faster airflow through a DPI results in better aerosol production.
Air and Drug Particle Movement through an Inhaler during a Fast Inhalation.
This is because it is the movement of air that both picks up the medication and creates an aerosol from it inhaling too slowly through the device will
a) Create an aerosol with more large particles, and less small ones
b) Leave more of the dose behind, in the inhaler and mouthpiece
It can be explained that without the fast flow of air through the inhaler, less of the dose will be picked up by the airflow, and what is carried away, will not be caught up in turbulent airflows that would normally ensure the large particles are broken up into the more desirable smaller particles.
Air and Drug Particle Movement through an Inhaler during a Slow Inhalation.
This flow dependency is more marked for some dry powder inhalers than others; better designs of DPI's produce a relatively consistent output over a wide range of airflows through them, as opposed to others where dose output can be reduced by 50% when the airspeed through them is not optimum.
Factors such as formulation (the way the dry powder medication is made), metering (the way in which the individual dose is made ready for inhalation) and inhaler design (materials used, dimensions, aerodynamics) all affect how each inhaler performs at different inhalation flows.
Summary
Airspeed is an important influence on both how well an aerosol travels into the lung, and the quantity and quality of drug aerosol generated from Dry Powder Inhalers.
Whilst aerosol dose and particle size from other types of device may not change significantly, no matter how fast the patient inhales (e.g. Metered Dose Inhalers, Soft Mist inhalers, and nebulisers), little of the aerosol produced may reach the target site in the lungs if the inhalation is at the wrong speed.
