Importance of Particle Size For Nebulized Medication

The physics of inhaled pharmaceutical aerosols (IPAs) is complex and involves aerosol mechanics, multiphase fluid mechanics, transport phenomena, and interfacial science, (in addition to pharmaceutics, chemistry, physiology, and medicine). Present understanding and prediction of the behaviour of IPAs remains relatively undeveloped.

Many researches are aimed at exploring and controlling the physics of inhaled pharmaceutical aerosols. Such aerosols are used in the therapeutic nebulized medication treatment of lung and respiratory diseases such as asthma, cystic fibrosis and even sinusitis, but are also being developed for the treatment of many other diseases where traditional delivery methods suffer drawbacks. Examples of the latter include pain management, as well as vaccinations using inhaled aerosols.

It is important to develop and improve the understanding and prediction of IPAs for the treatment of nose, sinus or lung disease using a mix of experimental, theoretical and numerical methods. One major factor to consider in areosolized treatments is the the importance of particle size of nebulized medication.

When the sinus or lung is the target for the aerosol, the inhaled aerosol must consist of particles in a certain size range. This is because particles larger than a certain size tend to simply land in the mouth and throat and mostly do not make it into the target destination. Particles somewhat smaller than a certain size tend to get inhaled and then exhaled right back out, while very small particles usually can’t be made in high enough numbers to give high enough dosages.

In a study on the differential deposition of aerosols in the maxillary sinus of human cadavers by particle size (by Christopher Hilton, M.D.,Timothy Wiedmann, Ph.D., Michele St. Martin, M.D., Bradley Humphrey, B.S., Rob Schleiffarth, B.A. and Frank Rimell, M.D.), there was a statistically significant difference in deposition among particle sizes.

The importance of particle size for nebulized medication is seen in the ff:

• Inhaled pharmaceutical aerosols (IPAs) are usually designed to produce drug particles each having the incredibly small mass of between approximately 1 trillionth and 100 trillionths of a gram.

• For particles with densities near that of water, this corresponds to particle diameters of a few millionths of a meter (i.e. a few micrometers). The probability that inhaled droplets of different diameters will deposit in the mouth-throat and tracheobronchial and alveolar regions of the lung for a particular aerosol, will be different for a another aerosol and cannot be used to evaluate other aerosols.

• Although specific size ranges are often quoted as being ideal for IPAs (e.g. 1-5 micrometers in diameter), significant amounts of particles outside this size range can still deposit in the lung, so that these size ranges should not be viewed as strict criteria. This is partly because the speed of the inhaled air plays a significant role in determining what size of particles will deposit where in the respiratory tract. For instance, someone breathing very slowly may cause larger particles to make it deeper in the sinus or lung than someone inhaling very rapidly.

• In addition, the filtering for particle deposition are slowly varying functions of particle size, and do not give ideal “bandpass” filtering of particle size.

• Finally, droplet evaporation or condensation can be different for different aerosols and result in different deposition patterns with different aerosols.