Supercritical anti-solvent

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. 

Finally, the industrial application of a technique based on the precipitation by a supercritical anti-solvent is discussed it can be economically attractive only with high-value products, such as pharmaceutical ones. 

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

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. 

An exhaustive review on particle formation by supercritical anti-solvent precipitation has recently been presented by Reverchon [44],... 

Won, D. H., M. S. Kim, S. Lee, J. S. Park, and S. J. Flwang. 2005. Improved physicochemical characteristics of felodipine solid dispersion particles by supercritical anti-solvent precipitation prtratess. 

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

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). 

Particle precipitation by Supercritical Anti-Solvent (SAS) according to various implementations like the batch Gas-Anti-Solvent (GAS) (48,49) and the continuous Aerosol Solvent Extraction System (ASES) (32,50-54) or Solvent Enhanced Dispersion by Supercritical fluids (SEDS) (30,31,55)... 

A supercritical anti-solvent precipitation technique has been used to prepare a novel Titania catalyst support. The Titania precursor was prepared by precipitating TiO (acac)2 from a solution of methanol using supercritical carbon dioxide at 110 bar and 40°C. The surface area of the supercritical precursor was 160 m g and this decreased to 35 mV after calcination, although there was no significant reduction of particle size. The new titania support was used to prepare a supported gold catalyst and this was tested for ambient temperature carbon monoxide oxidation. The supercritical catalyst demonstrated notably high activity when compared with catalysts prepared by other nonsupercriticd methods. 

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). 

Boonnoun, R, Nerome, H., Machmudah, S., Goto, M., and Shotipruk, A. Supercritical anti-solvent micronization of marigold-derived lutein dissolved in dichloromethane and ethanol. The Journal of... 

Yang, L., Sun, Z., Zu, Y, Zhao, C., Sun, X., and Zhang, Z. Physicochemical properties and oral bioavailability of ursolic acid nanoparticles using supercritical anti-solvent (SAS) process. Food Chemistry 132 (2012) 319-325. 

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. 

Mezzomo, N., Paz, E.d., Maraschin, M., Martin, A., Cocero, M.J., and Ferreira, S.R.S. Supercritical anti-solvent precipitation of carotenoid fraction from pink shrimp residue Effect of operational conditions on encapsulation efficiency. The Journal of Supercritical Fluids, 66 (2012) 342-349. 

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. 

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. 

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. 

In GAS or SAS, a batch of solution is expanded by mixing it with a supercritical fluid in a high-pressure vessel (Figure 24.6). Due to the dissolution of the compressed gas, the expanded solvent exhibits a decrease of the solvent power. The mixture becomes supersaturated and the solute precipitates in the form of microparticles. As shown in Figure 24.6, the precipitator is partially filled with the liquid solution of solid substance. The supercritical anti-solvent is then pumped up to desired pressure and introduced into the vessel, preferably from the bottom in order to achieve a better mixing of the solvent and anti-solvent. After a specified residence time, the expanded solution is drained under isobaric conditions in order to clean the precipitated particles. In this mode of operation, the rate of supercritical anti-solvent addition can be an important parameter in controlling the morphology and the size of solid particles. 

The protein-polymer microcapsules can be obtained by supercritical anti-solvent techniques [8]. Homogeneous protein-polymer mixtures were contacted with supercritical carbon dioxide in order to produce microspheres with diameter ranging from 1 to 5 pm and containing around 80% of protein. Production of PLA microparticles containing insulin, lysozyme, and chemotrypsin is claimed. SAS crystallization of a pharmaceutical (naproxen) and a biodegradable poly(L-lactic acid) was reported [8]. The results from SAS studies showed very small spherical particles... 

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