Supercritical fluid anti-solvent

Krukonls, V. J., Coffey, M. P., Gallagher, P. M. Exploratory Development on a New Process to Produce Improved RDX Crvstsls L Supercritical Fluid Anti-Solvent Recrystallization. Phasex Corp. Final Rept. to U.S. Army Ballistics Research Laboratory, 1988, Contr. DAAA15-86-C-007. 

The most important limitation of RESS is the low solubility of compounds in supercritical fluids and the use of co-solvent to improve solubility is usually costly and not economically feasible. As an alternative a supercritical fluid anti-solvent (SAS) process was introduced where a supercritical fluid is used to cause substrate precipitation or recrystallization from a polar liquid solvent (Subramaniam et ah, 1999). Zhong et ah (2008) successfully used SAS to produce alcohol soluble zein micro- and nanoparticles. A number of other technologies based on manipulating supercritical fluids have been successfully used to produce nanoparticles (Della Porta and Reverchon, 2008 Matsuyama et ah, 2003 Meziani and Sun, 2003 Shariah and Peters, 2003 Subramaniam et ah, 1999). 

Yeo, S. D., Lim, G. B., Debenedetti, P. D., and Bernstein, H. (1993) Formation of microparticulate protein powder using a supercritical fluid anti-solvent. Biotechnol. Bioeng. 41, 341-346. 

Mcrospfiere formation and encapsulation by the Gas AnthSolvenl (GAS) or Supercritical fluid Anti-Solvent (SAS) method... 

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. 

This process is also called supercritical fluid anti-solvent (SAS). Here, supercritical fluid is added to a solution of shell material and the active ingredients and maintained at high pressure. This leads to a volume expansion of the solution that causes supersaturation such that precipitation of the solute occurs. Thus, the solute must be soluble in the Hquid solvent, but should not dissolve in the mixture of solvent and supercritical fluid. On the other hand, the liquid solvent must be miscible with the supercritical fluid. This process is unsuitable for the encapsulation of water-soluble ingredients as water has low solubility in supercritical fluids. It is also possible to produce submicron particles using this method. 

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. 

Magnan C, Badens E, Commenges N, Charbit G. Soy lecithin micronization by precipitation with a compressed fluid anti-solvent—influence of process parameters. J Supercrit Fluids 2000 19 69-77. 

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. 

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. 

U. Foerter-Barth, U. Teipel, and H. Krause, Formation of particles by applying the gas anti-solvent (GAS) process, in Nottingham, 1999 Supercritical fluids Chemistry and Materials, Institut National Polytechnique de Lorraine, pp. 175-180. 

Micronization with supercritical fluids - Crystallization - Rapid expansion - Gas anti-solvent Recrystallization - Precipitation with compressed anti-solvent - Solution-enhanced dispersion - Particles from gas-saturated solutions 80 - 300 fine particles and powders from various products and of designed properties... 

The application of supercritical fluids as anti-solvents is an alternative recrystallization technique for processing solids that are insoluble in SCF. This method exploits the ability of gases to dissolve in organic liquids and to lower the solvent power of the liquid for the compounds in solution, thus causing the solids to precipitate. 

Supercritical fluids can be used to extract substances from natural products, as solvents or as anti-solvents to micronize drugs and biodegradable polymers, encapsulate drugs in polymeric matrices, resolve racemic mixtures of pharmacologically active compounds, fractionate mixtures of polymer and proteins, and sterilize bacterial organisms. 

Gallagher P., Coffey M, Krukonis V., Gas Anti-Solvent Recrystallization of RDX Formation of Ultra-fine Particles of a Difficult to Comminute Explosive, The Journal of Supercritical Fluids, No. 5, pp. 130-142, 1992... 

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

The mixed-crystal system formed by indomethacin and saccharin (l,2-benzisothiazol-3(2H)-one-l,1-dioxide) has been used to evaluate the feasibility of using supercritical fluids as media for the design and preparation of new cocrystals [44]. In this work, the relative merits of supercritical fluid processes (i.e., cocrystallization with a supercritical solvent, supercritical fluid as anti-solvent, and the atomization and anti-solvent technique) were evaluated, as well as the influence of processing parameters on product formation and particle properties of the yields. It was reported that while the anti-solvent and atomization procedures yielded pure cocrystal products, only partial to no cocrystal formation took place when using the crystallization process. 

Supercritical fluids have been shown to be excellent recrystallization agents for a variety of materials, and their use in recrystallizing an explosive, nitroguanidine (NQ), is presented. A new process, GAS (gas anti-solvent) Recrystallization, is described. 

Gallagher PM, Coffey MP, Krukonis VJ, Klasutis N. Gas anti-solvent recrystallization new process to recrystallize compounds insoluble in supercritical fluids. In Johnston KP, Penniger JML, eds. Supercritical Fluid Science and Technology. Washington, DC American Chemical Society, 1989 334-354. Dixon D, Johnston KP, Bodmeier R. Polymeric materials formed by precipitation with a compressed fluid antisolvent. AIChE J 1993 39 127-136. Chattopadhyay P, Gupta RB. Production of griseofulvin nanoparticles using supercritical CO2 antisolvent with enhanced mass transfer. Int J Pharm 2001 228 19-31. 

Thiering R, Dehghani F, Foster NR. Current issues relating to anti-solvent micronisation techniques and their extension to industrial scales. J Supercrit Fluids 2001 21 159-177. 

Weber A, Nolte C, Bork M, Kummel R. Recovery of lecithin from egg yolk-extracts by gas anti-solvent crystallization. Proceedings of the 6th Meeting on Supercritical Fluids Chemistry and Materials. 181-184. 

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)... 

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... 

Gallagher P.M., Coffey M.P., Krukonis V.J., KlasutisN., Gas Anti-Solvent recrystallization new process to recryst lize compounds insoluble in supercritical fluids. Supercritical fluid science and technology, Johnston K.P., Penninger J.M.L., 1989, (406), 334-354,. 

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. 

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