Medical and Pharmaceutical Aerosols - Aerosols: Measurement, Dosimetry, and Health Effects - page 11

temperature of the nebulized solution and may be detrimental for proteins and thermolabile drugs.
Ultrasonic nebulizers are less popular than jet nebulizers because they are more expensive and not
disposable. A common problem with ultrasonic nebulizers is that continuous atomization does not
occur if the volume in the chamber falls below 10 mL. 91 Detailed information on these mechanisms
of aerosolization has been described elsewhere. 102,103 A newer nebulizer design uses a vibrating
mesh or plate. Several advantages include faster nebulization (shorter treatment times), increased
eficiency (less drug needed), lower ill volume, and less heating of the nebulized solution. 104,105
Some factors that inluence nebulizer performance and droplet size are density and velocity of
the atomizing air, surface tension and viscosity of liquid, concentration, temperature, and nebulizer
design. 102 Eficiency of nebulizers is often expressed in terms of energy use, function, or output.
Output can be measured by simply weighing nebulizer before and after operation. Variation in total
output, particle size, and overall eficiency has been reported between different nebulizers. Several
studies have evaluated the differences between nebulizers. Chan et al. examined the aerosol charac-
teristics of ive handheld nebulizers in terms of aerosol output and droplet size. 106 Smith et al. tested
the variability among 23 different nebulizer/compressor combinations in terms of MMD, 107 while
Weber et al. optimized the nebulizer conditions of several nebulizers used to administer antibiotics
for the treatment of cystic ibrosis. 108
1.3.3.1 Solutions
Nebulizers are commonly used with solutions of bronchodilators, such as albuterol or terbutaline
and other drugs like sodium cromoglycate, corticosteroids, and pentamidine. 109,110 Cystic ibrosis
treatment with antimicrobials has become common as well. 94,111-113 Combinations of drugs could
be administered at the same time; however, the stability and possible interactions of the compo-
nents should be evaluated before administration. 114 A possible outcome can be an insoluble complex
in certain conditions. Interactions during nebulization of amiloride hydrochloride and nucleotide
UTP have been documented. 115 Other factors that should be accounted for are the effects that some
excipients included in the solution to be nebulized may have on the patient. Inclusion of preserva-
tives in the solutions of bronchodilators has been reported to cause bronchoconstriction instead and
the addition of osmotic agents may also cause side effects. 16,100,116-118 The effect of other additives,
ionic strength, and contamination could also inluence the effect of the nebulized solution. 119
1.3.3.2 Suspensions
Insoluble or inert particles can be suspended in a solution and delivered by nebulization provided
that the particle size is smaller than the droplet size and the density of the particle is relatively
small. Most steroids are not soluble in water and, therefore, have to be administered as suspensions.
It is important to note that when nebulized, suspensions of drugs behave differently than solutions.
Cameron et al. 120 compared the performance of ive different nebulizers with an amino-phylline
aerosol solution and a suspension of budesonide. They found that even with the same nebulizer,
different aerosol characteristics were obtained after nebulization of the solution and the suspension.
Tiano and Dalby determined how the differences in aerosolization mechanism (jet vs. ultrasonic)
affected droplet and insoluble particle deposition of a nebulized model respiratory suspension. Both
nebulizers produced droplets large enough to incorporate <6 μm insoluble latex spheres. However,
droplets generated by the jet nebulizer contained spheres of all sizes, while with ultrasonic nebu-
lizer, 99% of the spheres were not aerosolized and recovered from the nebulizer. 121
Liposomal formulations have also been delivered by nebulization. 122-126 Effects of air pressure,
temperature, buffer, osmotic strength, and pH on the nebulized liposome dispersions were studied.
Changes in air pressure produced large changes in the percentage of release of the encapsulated
substance; increasing air pressure increased the percentage of release. The leakage of liposomes
was increased in hypotonic solution but decreased in hypertonic solution. At low pH, the leakage
was increased compared to higher pH. Stability of liposomes was affected by the operating and
environmental conditions of aerosolization, with air pressure having the greatest effect. 122 Droplet