MEDICINAL AEROSOLS

Aerosol Aerosol
An aerosol is a colloid of fine solid particles or liquid droplets, in air or another gas.
therapy plays an extremely important part in the treatment of diseases of the respiratory tract. When it is inhaled, the active agent is delivered directly to the "scene of the action", which means that many systemic side effects can be avoided or at least considerably reduced.

In order for the aerosol aerosol
An aerosol is a colloid of fine solid particles or liquid droplets, in air or another gas.
to work to its best effect, several key factors must be considered:

Deposition of the aerosol in the lungs

The deposition of aerosols in the respiratory tract is determined by three factors: impaction, sedimentation and diffusion. The relative importance of each depends on the particle size and the respiratory flow rate.

Impaction

Impaction is the term used for the deposition of the aerosol aerosol
An aerosol is a colloid of fine solid particles or liquid droplets, in air or another gas.
particle in the lung due to its mass inertia. While particles that are small and inhaled slowly can often follow the inspiratory flow inspiratory flow
Indicate the volume inspired from the nebuliser, simulated during an in vitro analysis.
unhindered as the passages branch and become narrower, larger, faster particles usually become trapped there.  A large proportion of aerosols with a diameter > 3µm is deposited due to impaction regardless of the air flow.

Sedimentation

This form of deposition is dependent on gravity, and it takes effect during the inspiratory pause, when the prevailing factor of the flow is diminished. It takes place according to particle size – larger particles succumb to sedimentation more quickly than smaller particles. Since the largest particles have already been filtered out in the upper regions of the respiratory tract as a result of impaction, the process of sedimentation has the greatest effect on particles between 1 and 4µm in size.

Diffusion

Without an airstream, most particles smaller than 1µm move randomly, subject to the principles of Brownian molecular motion. They are hardly involved in the sedimentation process at all because of their extremely small weight. As a result, they can remain suspended even during inspiratory pause, and most are breathed out again with the next expiratory breath. A relatively small fraction comes to rest on the surface of the lung during diffusion and is deposited there.

In general, deposition in the deep lung is increased if the inspiratory volume is large and the patient breathes in slowly.

Targeting

If the active agent is to be delivered to the upper respiratory tract, that is the nasal and throat cavity (extrathoracic deposition), an inhalation system that generates an aerosol aerosol
An aerosol is a colloid of fine solid particles or liquid droplets, in air or another gas.
in the size range from 8 - 10µm must be selected. The patient should also breathe in as rapidly as possible.

To deposit the medication in the central regions of the lungs, an aerosol aerosol
An aerosol is a colloid of fine solid particles or liquid droplets, in air or another gas.
with particle sizes in a range from 4 - 8µm must be created. In this case, the patient should take care to breathe in slowly to avoid depositing the medication in the area of the larynx.

For alveolar deposition, the droplets must be considerably smaller, i.e., with an MMAD of 3 - 4µm. The patient should inhale slowly to minimise the quantity of larger droplets being deposited in the throat region. Pausing at the end of inspiration increases the probability of alveola­r deposition.

For a systemic application, the aerosol aerosol
An aerosol is a colloid of fine solid particles or liquid droplets, in air or another gas.
droplets must be smaller than 3-4µm.

Factors affecting nebuliser therapy efficiency

The quantity of any substance that is actually effective in the respiratory tract is affected by a number of factors, which in turn depend on the medication, the nebuliser performance, and the patient himself.

Factors affecting nebuliser therapy efficiency
MedicationNebuliserPatient
ConcentrationParticle size distributionRespiratory flow rate
Solubility in waterTotal outputInspiratory volume
ViscosityDose administeredRespiratory tract morphometry
HygroscopyRespirable dose Respirable dose
The amount of respirable drug (Particle size < 5 µm) that is supplied from the inhalation system.
Degree of obstruction obstruction
Increased resistance in the airways that reduces the amount of air inhaled in each breath and the oxygen that reaches the pulmonary arteries.
VolumeAerosol Aerosol
An aerosol is a colloid of fine solid particles or liquid droplets, in air or another gas.
density
Compliance

Important parameters of nebuliser performance

Droplet size

In order to ensure that medications for treating respiratory tract diseases reach the site where their action can be most effective (targeting), the properties of the aerosol aerosol
An aerosol is a colloid of fine solid particles or liquid droplets, in air or another gas.
must be correct. The sizes of the particles in the aerosol aerosol
An aerosol is a colloid of fine solid particles or liquid droplets, in air or another gas.
and the spectrum in which these sizes are distributed as well as the mass of the medication that is transported are all fundamental characteristics that determine the regions of the respiratory tract that can be reached and the therapeutic effects that can be achieved. The distribution of active agent quantity over the particle size is thus of primary interest. Two values that can be determined experimentally are useful here: the mass median diameter (MMD MMD
Mass median diameter – The mass median diameter (MMAD) is the diameter such that half the aerosol particles is contained in particles with larger diameter and half the particles with smaller diameter, i.e. M normalized (MMD)=1/2.
)
and the mass median aerodynamic diameter (MMAD). Half of the mass of the particles has a smaller diameter than the MMD MMD
Mass median diameter – The mass median diameter (MMAD) is the diameter such that half the aerosol particles is contained in particles with larger diameter and half the particles with smaller diameter, i.e. M normalized (MMD)=1/2.
/MMAD, the other half of the mass consists of particles with a larger diameter than the MMD MMD
Mass median diameter – The mass median diameter (MMAD) is the diameter such that half the aerosol particles is contained in particles with larger diameter and half the particles with smaller diameter, i.e. M normalized (MMD)=1/2.
/MMAD.

The MMD MMD
Mass median diameter – The mass median diameter (MMAD) is the diameter such that half the aerosol particles is contained in particles with larger diameter and half the particles with smaller diameter, i.e. M normalized (MMD)=1/2.
refers to a static aerosol aerosol
An aerosol is a colloid of fine solid particles or liquid droplets, in air or another gas.
mist and can be determined relatively quickly and easily by laser diffraction. The mass median aerodynamic diameter (MMAD) refers to the behaviour of the particles in an air flow and is therefore an extremely significant value for the purposes of inhalation treatment. It is determined by cascade impaction, the experimental setup for which is considerably more complex than laser diffraction. Since the MMD MMD
Mass median diameter – The mass median diameter (MMAD) is the diameter such that half the aerosol particles is contained in particles with larger diameter and half the particles with smaller diameter, i.e. M normalized (MMD)=1/2.
and MMAD of aqueous solutions are usually identical (e.g. salbutamol), reliable values for MMAD can also be calculated with laser diffraction1. In many cases, a correlation can also be established between MMD MMD
Mass median diameter – The mass median diameter (MMAD) is the diameter such that half the aerosol particles is contained in particles with larger diameter and half the particles with smaller diameter, i.e. M normalized (MMD)=1/2.
and MMAD for suspensions with particles having a significantly different shape and density than water. 

Aerosols are generally made up of droplets that have different diameters. One measurement of the distribution of particle sizes is the standard deviation from the MMD MMD
Mass median diameter – The mass median diameter (MMAD) is the diameter such that half the aerosol particles is contained in particles with larger diameter and half the particles with smaller diameter, i.e. M normalized (MMD)=1/2.
/MMAD (GSD = geometric standard deviation). The larger the GSD, the wider the distribution. Aerosols with a GSD up to 1.15 are called monodisperse, if their GSD is greater than 1.15 they are polydisperse. Most commercial nebulisers deliver aerosols with a GSD of about 2.

1) Bitterle et al. . International Society of Aerosols in Medicine (ISAM), 16th International Congress, Tours, France, June 16 – 20, 2007: Correlation of laser diffraction and cascade impaction data upon nebulisation of 1MIU colistimethate sodium/3ml by the eFlow®rapid nebulizer