Supercritical fluid process 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). 

Supercritical fluid crystallization (SFC) is a technique for precipitating or crystallizing solutes dissolved in liquid solvents by injecting or mixing the solvent system with a compressed or supercritical fluid antisolvent. SFC is unique in that it uses a compressed gas to trigger the crystallization. Two benefits often associated with SFC include single-step processing of particulate pharmaceuticals with controlled... 

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]. 

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... 

PCA [Precipitation with a Compressed Antisolvent] 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... 

Most drugs and proteins are not soluble in commonly used supercritical fluids, and therefore are processed instead by the SC antisolvent technique,the most popularized being the SEDS, process which is illustrated in Fig. 9. SEDS-produced crystals can have extremely smooth surfaces, as shown by scanning electron microscopy and atomic force microscopy, and the surface may be more hydrophobic and less wettable than crystals grown under more polar conditions.A scanning electron micrograph of acetominophen crystals produced by the SEDS process is shown in Fig. 10. 

Mass transfer is also favored by the high diffusivity that characterizes supercritical fluids. The difference in density between the liquid and the antisolvent also plays a role in determining the direction of mass transfer. However, the SAS process does not seem to be substantially limited by mass transfer resistances. ... 

Thermodynamic constraints to the SAS process can be summarized in the required miscibility between the liquid solvent and the supercritical antisolvent and the insolubility of the solute in the antisolvent and in the solvent-antisolvent mixture. Data are available for various binary mixtures liquid-supercritical fluid and can be described as type I using the classification of van-Konynenburg and Scott. If jet break-up is obtained and mass transfer is very fast, high-pressure VLEs of the ternary system liquid-I-solute-I-supercritical fluid can control the precipitation process. 

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

Werling, J.O. Debenedetti, P.G. Numerical modeling of mass transfer in the supercritical antisolvent process miscible conditions. J. Supercrit. Fluids 2000, 18, 11-24. 

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). 

Reverchon E. Supercritical antisolvent precipitation its applications to microparticle generation and products fractionation. Proceedings of the 5th Meeting on Supercritical Fluids, Materials, and Natural Products Processing. Vol. 1. Nice France, 1998 221-236. 

Badilla JCDF, Peters CJ, Arons JDS. Volume expansion in relation to the gas antisolvent process. J Supercrit Fluids 2000 17(1) 13-23. 

Mukhopadhyay M. Purification of phytochemicals by selective crystallization using carbon dioxide as antisolvent. Proceedings of the 10th International Symposium on Supercritical Fluid Chromatography, Extraction and Processing, Myrtle Beach, SC, August 2001. 

Yeo Sang-Do, Kim Min-Su, Lee Jong-Chan. Recrystallization of sulfathiazole and chlorpropamide using the supercritical fluid antisolvent process. J Supercrit Fluids. In Press. 

Krober H, Teipel U. Materials processing with supercritical antisolvent precipitation process parameters and morphology of tartaric acid. J Supercrit Fluids 2002 22 229-235. 

Gallagher PM, Colfey MP, Krukonis VJ, Klasutis N. Gas antisolvent recrystallization new process to recrystallize compounds insoluble in supercritical fluids. In Penniger JML, ed. Supercritical Fluid Science and Technology. ACS Symposium Series 406. Washington, DC American Chemical Society, 1989 334-354. 

Weber A, Tschernjaew J, Kummel R. Coprecipitation with compressed antisolvents for the manufacture of microcomposites. Proceedings of the 5th meeting on Supercritical Fluids Materials and Natural Products Processing, Nice,... 

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

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. 

Supercritical fluids, such as CO2, often exhibit weak solvent strength toward many organic and polymeric solutes. This antisolvent or nonsolvent nature of these SCFs for many solutes can further be employed by spraying an organic solution of the drug and/or polymer through a nozzle into a compressed gas or SCF (Figure 2). This process, termed precipitation with... 

Abbreviations A, acetone ASES, aerosol solvent extraction system DM, dichloromethane DMF, A/,A/-dimethyl-formamide E, ethanol GAS, gas antisolvent process H, hexane HYAFF-11, hyaluronic acid benzylic ester I, isopropanol PAN, polyacrylonitrile PCA, precipitation with compressed antisolvent PCL, polycaprolactone PHB, poly(p-hydroxybutyric acid) PLA, polylactic acid PLGA, poly(lactic-co-glycolic acid) SAS, supercritical antisolvent process SEDS, solution enhanced dispersion by supercritical fluids TFE, 2,2,2-trifluoroethanol Triblock polymer, p poly(L-lactide-CO-D,L-lactide-co-glycolide)(62.5 1 2.5 25). 

Using Supercritical Fluid Antisolvent Techniques in Phospholipid Processing... 

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. 

Kikic I, Bertuco A. Thermodynamic and mass transfer for the simulation of recrystallization processes with a supercritical antisolvent. Proceedings of the 4th Italian Conference on Supercritical Fluids, 1997 299-306. 

Jung J, Clavier JY, Perrut M. Gram to kilogram scale-up of supercritical fluid antisolvent process. Proceedings of the 6th International Symposium on Supercritical Fluids, 2003 1683-1688. 

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