Aerosol particles, rapid expansion

Rapid expansion from supercritical to aqueous solution to produce submicron suspensions of water-insoluble drugs. Biotechnol Prog 2000 16 402 07. Helfegen B, Hils P, Holzknecht Ch, Tiirk M, Schaber K. Simulation of particle formation during the rapid expansion of supercritical solutions. Aerosol Sci 2001 32 295 319. 

Berends EM, Bruinsma OSL, VanRosmalen GM. Nucleation and growth of fine crystals from supercritical carbon dioxide. J Crys Growth 1993 128 50-56. Cihlar S, Turk M, Schaber K. Submicron particles of organic solids by rapid expansion of supercritical solutions. J Aerosol Sci 1999 30 355-356. 

As described in Chapter 3, several SCF techniques are available for the preparation of drug delivery systems. These include rapid expansion of supercritical solutions (RESS), gas antisolvent recrystallization (GAS), supercritical antisolvent recrystallization (SAS), supercritical antisolvent with enhanced mass transfer (SAS-EM), solution-enhanced dispersion by supercritical fluids (SEDS), supercritical fluid nucleation (SFN), precipitation with compressed antisolvent (PCA), and aerosolized supercritical extraction of solvents (ASES). While RESS and SFN involve the expansion of a supercritical fluid solution of a drug to form drug particles, GAS, SAS, SAS-EM, SEDS, PCA, and ASES use a supercritical fluid as an antisolvent to precipitate particles of a drug dissolved in an organic solvent (5). General RESS and GAS processes are further elaborated in Sections 1.1.1 and 1.1.2. 

The principle of all aerosols is that a liquefied gas in a pressurised container will provide a constant pressure while the container is being emptied. The essential components of an aerosol beside the container itself are the product, propellant, and valve assembly. The valve is designed to dispense the product in the required manner while maintaining both the product and propellant hermetically sealed until the product is expended. The fact that the product is sealed in the container and protected from air and other outside contaminants has obvious advantages in the field of pharmaceuticals. The intimate mixture of propellant and product in a true aerosol results in a rapid expansion of the propellant as it leaves the valve orifice. This breaks up the product into small particles giving a fine mist, coarse spray, foam, or dust according to the nature and relative quantity of the product and the propellant and the type of valve. 

Some common size range descriptions for atmospheric aerosol particles and droplets are shown in Tables 1.5 and 1.6. These ranges and descriptions are based mostly on the techniques used to determine the sizes [122,124,125]. Aitken particles and droplets (diameters less than 0.2 pm) are typically detected using an Aitken nucleus counter (also called a Nolan-Pollak counter or a Poliak counter). Here, the aerosol is introduced into a chamber containing vapour-saturated gas. Rapid volume expansion and adiabatic cooling are used to induce supersaturation in the gas, which in turn causes condensation on the original particles, which act as nuclei [122, 125]. This makes the original, small particles or droplets easy to observe and count with a microscope. (The principle just described is somewhat similar to the operation of a Wilson cloud chamber (see Section 7.1.4).)... 

In the condensation method, a sample of vapour-saturated gas is subjected to a rapid volume expansion. This lowers the temperature and causes a state of supersaturation. Condensation of the vapour will then take place on any particles or ions present in the sample. If the sample is free of particles and ions, there will still be collisions of vapour molecules that create clusters, called embryos, which can serve as nuclei for condensation. Although the seeding nuclei maybe of different sizes, they grow by diffusion of the condensable vapour to ultimate diameters that are almost independent of the original nuclei sizes. The condensation method can be used to make aerosols having diameters from about 36 nm to just over 1 pm and concentrations from about 10 to 10 particles/cm [64]. 

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