Ultrasound-assisted aerosolization

Pulmonary administration of pharmaceutioal oompounds using aerosols is a oommon olinioal practice due to its relatively easy use. It is generally accepted that aerosol particles of 1-5 pm in size are required for deposition in the alveolar region of the lung, which exhibits the highest systemic absorption however, particles less than 1 pm in diameter are more easily incorporated into the respirable percentage of aerosolized droplets. 

Aerosol droplet size is influenced by physical variables such as surface tension, viscosity, saturated vapour pressure and temperature. A decrease in the first three decreases droplet size. Because a decrease in temperature increases all three variables, it also increases the difficulty of aerosol formation. Droplet diameter is related to the US frequency [155] and other physical parameters by the following equation  

The use of surfactants to modify the surface tension of an aerosol and alter its droplet size distribution has shown that their influence depends strongly on the characteristics of the solution to be aerosoled. The span, defined as 90% undersize —10% undersize/50% undersize, gives a measure of the width of the volume distribution relative to the median diameter of the droplets formed in the aerosoling process. Comparative studies performed with commercial air-jet and US nebulizers have shown that, under similar working conditions, the latter provide less heterodispersed aerosols, with span values ranging from 1.50 to 1.75, which are similar for aqueous drug solutions in the presence and absence of surfactants [156]. 

One undesirable size-effect of aerosolization is droplet aggregation, which has been shown to result from increased hydrophobicity in the nanoparticles formed in an air-jet device, but not in US-assisted devices, whether particles are hydrophobic or hydrophilic [157]. 

Recent studies on aerosol formation by using air-jets and ultrasonication prior to the determination of complex size and zeta potential revealed that neither type of device destabilized the compounds studied (viz. polyethylenimines), even though droplet size was found to increase upon air-jet aerosoling [158]. 

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Ultrasound assisted aerosol formation or nebulization prior to sample insertion into an atomic detector is dealt with in Chapter 8 on the grounds of its close relationship to the instrument in spatial and temporal terms. Also, as a step of spray drying, known as "atomization ", is discussed in Chapter 2 inasmuch it can be used for sample conservation purposes and hence as an analytical operation preceding sample preparation. This section is concerned with other non-analytical uses of US-assisted aerosol formation that are closely related to the analytical field and can open new avenues for the development of previously unexplored analytical uses. 

Some of the reports are as follows. Mizukoshi et al. [31] reported ultrasound assisted reduction processes of Pt(IV) ions in the presence of anionic, cationic and non-ionic surfactant. They found that radicals formed from the reaction of the surfactants with primary radicals sonolysis of water and direct thermal decomposition of surfactants during collapsing of cavities contribute to reduction of metal ions. Fujimoto et al. [32] reported metal and alloy nanoparticles of Au, Pd and ft, and Mn02 prepared by reduction method in presence of surfactant and sonication environment. They found that surfactant shows stabilization of metal particles and has impact on narrow particle size distribution during sonication process. Abbas et al. [33] carried out the effects of different operational parameters in sodium chloride sonocrystallisation, namely temperature, ultrasonic power and concentration sodium. They found that the sonocrystallization is effective method for preparation of small NaCl crystals for pharmaceutical aerosol preparation. The crystal growth then occurs in supersaturated solution. Mersmann et al. (2001) [21] and Guo et al. [34] reported that the relative supersaturation in reactive crystallization is decisive for the crystal size and depends on the following factors. 

Ultrasound-assisted nebulization is largely used in the clinical field, where the word "aerosolization" or "aerosoling" is used preferentially over "nebulization", and industrial field, where "US-assisted nebulization" and "US-assisted spraying" are preferred. 

Ultrasonic nebulization is known to provide a higher analyte transport efficiency than pneumatic nebulization (normally 8-15 times higher) this results in improved sensitivity and lower detection limits, which is especially important for the analysis of species at trace or ultratrace levels [31-35]. Ultrasound-assisted generation of smaller drops and the use of a desolvation system to remove most of the solvent load allow the production of fine, dry analyte-enriched aerosol for insertion into a detection system some authors, however, ascribe most of the sensitivity increase of USNs to the desoivation system aione [36]. 

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