Supercritical anti-solvent process

Economical considerations are investigated in this section, with reference to high pressure extraction plants, to the production of polyethylene, and to the precipitation by supercritical anti-solvent process. 

The goal of this brief discussion is to understand the scenarios in which a supercritical anti-solvent process (SAS) could be economically feasible. 

Wang, Y., et al. (2004), Polymer coating/encapsulation of nanoparticles using a supercritical anti-solvent process, /. Supercrit. Fluids, 28, 85-99. 

Sui, X., Wei, W., Yang, L., Zu, Y., Zhao, C., and Zhang, L. Preparation, characterization and in vivo assessment of the bioavailability of glycyrrhizic acid microparticles by supercritical anti-solvent process. International Journal of Pharmaceutics 423 (2012) 471-479. 

Zhong, Q., Jin, M., Davidson, P.M., Zivanovic, S., 2009. Sustained release of lysozyme from zein microcapsules produced by a supercritical anti-solvent process. Food Chem. 115, 697-700. 

Supercritical anti-solvent micronization can be performed using different processing methods and equipment [17]. Different acronyms were used by the various authors to indicate the micronization process. It has been referred to as GAS (gas anti-solvent), PCA (precipitation by compressed anti-solvent), ASES (aerosol solvent extraction system), SEDS (solution enhanced dispersion by supercritical fluids), and SAS (supercritical anti-solvent) process [8,17]. Since the resulting solid material can be signiflcantly influenced by the adopted process arrangement, a short description of the various methods is presented below. 

The MMA fed to the reactor is converted to PMMA tiU a conversion of 15%. The product stream (2) consisting of PMMA, MMA and CO2, is sprayed into the extraction column, in which it is contacted with supercritical CO2 counter currently. The PMMA precipitates and the MMA dissolves in the supercritical phase. This extraction process is better known as the Supercritical Anti-Solvent process... 

Both the nucleation of supercritical anti-solvent bubbles in a polymer+organic solvent-rich phase in the supercritical anti-solvent process (SAS) (or, equivalently, precipitation with a compressed antisolvent PCA) (e.g., [76]) and the nucleation of bubbles of a dissolved supercritical fluid from a saturated and nozzle-expanded solution containing a solute to be precipitated, in the formation of particles from gas-saturated solutions (PGSS) [77] are bubble nucleation problems, to which the above ideas apply. In the latter case, the nucleation of bubbles occurs simultaneously with that of solid particles within the bulk supersaturated solution. 

Kikic, I., Bertucco, A. and Lora, M. (1997) Thermodynamic Description of Systems Involved in Supercritical Anti-Solvent Processes, The 4 International Symposium on Supercritical Fluids, Sendai, Japan, pp. 39-42. 

Hanna M, York P (1998) Method and apparatus for the formation of particles, Google Patents Jung J, Clavier JY, Perrut M (2003) Gram to kilogram scale up of supercritical anti-solvent process. 

The gas anti-solvent processes overcome the limited solvent capacity of supercritical gases for substances with high molecular weight by using a classical liquid solvent. 

Gas anti-solvent processes (GASR, gas anti-solvent recrystallization GASP, gas antisolvent precipitation SAS, supercritical anti-solvent fractionation PCA, precipitation with a compressed fluid anti-solvent SEDS, solution-enhanced dispersion of solids) differ in the way the contact between solution and anti-solvent is achieved. This may be by spraying the solution in a supercritical gas, spraying the gas into the liquid solution. 

In Tables 9.9-3 to 9.9-5 a summary of the recrystallization process of pharmaceuticals and bio-polymers, and co-precipitation by supercritical anti-solvent is presented. In Figures 9.9-1 and 9.9-2 examples of very long needle crystal and nano-particles are reported. 

Won D-H, Kim M-S, Lee S, ParkJ-S, and Hwang S-J. Improved Physicochemical Characteristics of Felodipine Solid Dispersion Particles hy Supercritical Anti-Solvent Precipitation Process. IntiJPharm 2005 301 199-208. 

Many of the unfolding processes are irreversible however, some are reversible with the return of full biological activity. For example, proteins dissolved in DMSO refold upon dilution in water (Chang et ah, 1991). Supercritical anti-solvent precipitation of insulin, lysozyme and trypsin from DMSO yielded partially unfolded intermediates, as characterized by spectroscopy (Yeo et al., 1994 Winters et ah, 1996). However, these structures were reversible upon reconstitution in aqueous media, with recovery of biological activity (Yeo et ah, 1994 Winters et ah, 1996). Chymotrypsin also completely unfolded in DMSO, but regained activity upon rehydration (Zaks and Klibanov, 1988a Yeo et ah, 1994). 

Supercritical anti-solvent and related processes (GAS/SAS/ASES/SEDS) In these processes, the SCE is used as an antisolvent that causes precipitation of the substrate(s) dissolved initially in a liquid solvent. This general concept consists of decreasing the solvent power of a polar liquid solvent in which the substrate is dissolved, by saturating it with carbon dioxide in supercritical conditions, causing the substrate precipitation or recrystallization. Depending on the desired solid morphology, various methods of implementation are available ... 

Low reactivity in general Reversible reactivity with weak nucleophiles (e.g. amines) Potential for product processing applications supercritical anti solvents, SAS rapid expansion of supercritical solution, RESS super fluid chromotography, SEC Reacts with strong nucleophiles... 

At high pressures a considerable amount of a gas can be dissolved in a liquid solution. Once dissolved in the liquid phase it may act as an anti solvent. In literature this type of drowning out is often referred to as the Gas Anti-Solvent (GAS) process, it is also known as the Supercritical Anti-Solvent (SAS) process or as Precipitation with a Compressed fluid Anti solvent (PCA). 

Wang, W., Liu, G., Wu, J., and Jiang, Y. Co-precipitation of 10-hydroxycamptothecin and poly (1-lactic acid) by supercritical C02 anti-solvent process using dichloromethane/ethanol co-solvent. The Journal of Supercritical Fluids 74 (2013) 137-144. 

Lesoin, L., Crampon, C., Boutin, O., and Badens, E. Preparation of liposomes using the supercritical anti-solvent (SAS) process and comparison with a conventional method. The Journal of Supercritical Fluids 57 (2011) 162-174. 

B. SAS — Supercritical Anti-Solvent Precipitation and Related Processes. 647... 

Supercritical fluid anti-solvent processes have been recently proposed as alternatives to liquid anti-solvent processes commonly employed in the industry. The key advantage of the supercritical processes over liquid ones is the possibility to completely remove the anti-solvent by pressure reduction. This step of the process is problematic in case of liquid anti-solvents since it requires complex post-processing treatments for the complete elimination of liquid residues. Furthermore, the supercritical anti-solvent is characterized by diffusivity that can be up to two orders of magnitude higher than those of liquids. Therefore, its very fast diffusion into the liquid solvent produces the supersaturation of the solute and the precipitation in micronized particles with diameters that are not possible to obtain using liquid anti-solvents or other methods. 

The routes to particle synthesis via supercritical fluids basically follow two paths. Rapid Expansion of Supercritical Solution (RESS) and Supercritical Anti-Solvent (SAS). The basic processing steps are outlined in Figure 21.18 and Figure 21.19, respectively. RESS involves homogenization of the particles raw material in the supercritical fluid followed by rapid expansion of the solution through an expansion device such as a nozzle. Depending on the nozzle design, time-temperature and time-pressure profiles, and whether one uses... 

Besides the supercritical fluid extraction (SFE) for preparation of medicines and materials processing, supercritical fluid technology involves processes such as supercritical anti-solvent (SAS), rapid expansion supercritical solutions (RESS), rapid expansion of a supercritical solution into a liquid solvent (RESOLV), supercritical assisted atomization (SAA), impregnation and solution enhanced dispersion by supercritical CO2 (SEDS) that involves the supercritical fluid in drug processing to drug delivery systems. 

Stephanie Careno, Olivier Boutin, Elisabeth Badens, Drug recrystallization using supercritical anti-solvent (SAS) process with impinging jets Effect of process parameters. Journal of Crystal Growth 342 (2012), p. 34-41. 

Gas [Gas anti-solvent] A process for separating dissolved materials by selective precipitation with added supercritical carbon dioxide. First used for recrystallizing the explosive RDX subsequently used for recrystallizing other explosives, pharmaceuticals, fine chemicals, and food products. 

PCA [Precipitation with a compressed anti-solvent] A process for making a solid with unusual morphology by spraying a solution of it into a supercritical fluid. The process resembles spray drying into a supercritical fluid. Used for making microspheres, microporous fibers, and hollow microporous fibers. 

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