Gas antisolvent

Gas AntisolventRecrystallizations. A limitation to the RESS process can be the low solubihty in the supercritical fluid. This is especially evident in polymer—supercritical fluid systems. In a novel process, sometimes termed gas antisolvent (GAS), a compressed fluid such as CO2 can be rapidly added to a solution of a crystalline soHd dissolved in an organic solvent (114). Carbon dioxide and most organic solvents exhibit full miscibility, whereas in this case the soHd solutes had limited solubihty in CO2. Thus, CO2 acts as an antisolvent to precipitate soHd crystals. Using C02 s adjustable solvent strength, the particle size and size distribution of final crystals may be finely controlled. Examples of GAS studies include the formation of monodisperse particles (<1 fiva) of a difficult-to-comminute explosive (114) recrystallization of -carotene and acetaminophen (86) salt nucleation and growth in supercritical water (115) and a study of the molecular thermodynamics of the GAS crystallization process (21). 

Dixon, J. and Johnston, K. (1991) Molecular thermodynamics of solubilities in gas antisolvent crystallization. AIChE Journal, 37 (10), 1441-1449. 

Gas analysis, of water, 26 36-40, 41-42 Gas antisolvent (GAS) technique, 24 17 Gas-assisted injection molding (GAIM), 19 552... 

A number of techniques are based on supercritical fluid technology. Three are of particular pharmaceutical interest, namely the supercritical antisolvent (SAS) system, the rapid expansion of supercritical solution (RESS) method, and the gas antisolvent (GAS) technique [126]. 

Gas antisolvent reciystallization where the supercritical fluid acts as an antisolvent for dissolved drug contained in droplets of another miscible or partially miscible liquid, for example, ethanol, methanol, or acetone. 

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. 

Fusaro, F., M., M. Flanchen, M. Mazzotti, G Muhrer, and B. Subramaniam. 2005. Dense gas antisolvent precipitation A comparative investigation of the GAS and PCAtechnidpi ng Chem Res44 1502-1509. 

Several new processes for formation of solid particles with defined particle size and particle size distribution using supercritical fluids were developed in the past years. Examples are crystallisation from supercritical fluids, rapid expansion of supercritical solutions (RESS), gas antisolvent recrystallisation (GASR), and PGSS (Particles from Gas Saturated Solutions)-process [1,2]. 

Production of fine, solvent free powders is of great importance in the pharmaceutical industry /5/. Conventional techniques produce particles with broad particle size distributions. Moreover, particles may be irregular or contain solvents. Hence the development of procedures such as Rapid Expansion of Supercritical Solutions (RESS) or the Gas Antisolvent Recrystallisation (GAS) is in progress /5, 6/... 

Gallagher P.M., Coffey M.P., Krukonis V.J., Klasutis N., Gas Antisolvent Recrystallisation New Process to Recrystallize Compounds Insoluble in Supercritical Fluids, ACS Symp. Ser. 406, 1989, 335-54... 

Randolph, T. W., RAndolph, A. D., Mebes, M., and Yeung, S. (1993), Submicrometersized biodegradable particles of poly(L-lactic acid) via the gas antisolvent spray precipitation process, Biotechnol. Prog., 9,429-435. 

Gas [Gas antisolvent] 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. Another use has been for precipitating insulin particles from dimethylsulfoxide solution. 

Fusaro, F. Mazzotti, M. Gas antisolvent recrystallization of paracetamol from acetone using compressed carbon dioxide as antisolvent. Cryst. Growth Des. 2004, 0 (0), 1-9. 

Gas Antisolvent Recrystallization New Process To Recrystallize Compounds Insoluble in Supercritical Fluids... 

Gas antisolvent processes can be performed in a semicontinuous mode. In this case the solution and the antisolvent are continuously introduced in the system until the desired amount of the product is formed. The introduction of the solution is then stopped and the DG flux extracts the residual solvent from the system. The system is then depressurized to enable collection of the product. The solution is generally introduced through an atomization nozzle that favors the prompt expansion of the solution and the formation of small particles. Different process configurations have been utilized, i.e., co- and countercurrent introduction of the solution and antisolvent fluxes and various nozzles have been designed. The process is referred to by different acronyms such as ASES (aerosol solvent extraction system), SAS (supercritical antisolvent), SEDS (solution enhanced dispersion by supercritical fluids), PCA (precipitation with a compressed fluid antisolvent), GASR (gas antisolvent recrystallization), GASP (gas antisolvent precipitation). 

Dense gas antisolvent techniques are amenable to the precipitation of proteins because of the low solubility of these compounds in DGs such as carbon dioxide. Lysozyme, trypsin, myoglobin, and insulin are examples of peptides that have been precipitated from organic solutions using CO2 as an antisolvent. Both batch and semicontinuous DG antisolvent techniques have been used to precipitate proteins from organic solvents such as methanol, ethanol, and dimethyl sulfoxide. ... 

Gas-Antisolvent arui Supercritical Fluid Antisolvent Method... 

An SCF can be used as an antisolvent, which will cause precipitation of a dissolved substrate from a liquid solvent. This approach, called the SAS (supercritical fluid antisolvent) or GAS (gas antisolvent) method, results in a pronounced volume expansion greater than with RESS, leading to supersaturation and then precipitation of the solutes. (Fig. 10). 

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