Supercritical fluid antisolvent

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... 

Yeo, S. Ltm, G.B. Debenedetti, P.G. Berstein, H. Formation of microparticulate protein powder using a supercritical fluid antisolvent. Biotechnol. Bioeng. 1993, 41, 341. 

GAS/SAS Gas or supercritical fluid antisolvent introduces gas or supercritical fluid to decrease the solvent power of a polar liquid solvent in which a substrate is dissolved causing substrate precipitation or recrystallization... 

Yeo SD, Lim GB, Debenedetti PG, and Bernstein H. Formation of Microparticulate Protein Powder using a Supercritical Fluid Antisolvent. Biotechnol Bioeng 1993 41 341-346. 

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). 

Figure 10 This GAS or SAS variant involves taking the solvent, drug, and polymer dissolution and then using an SCF as an antisolvent to produce the particles. Abbreviations GAS, gas antisolvent SAS, supercritical fluid antisolvent SCF, supercritical fluid. Source From Ref. 74.

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. 

Using Supercritical Fluid Antisolvent Techniques in Phospholipid Processing... 

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. 

Before ending this section it is informative to contrast the behavior of a liquid antisolvent and a supercritical fluid antisolvent. Cowie and McEwen (1974) show that a liquid antisolvent could also be added to the polymer solution to shift the LCST to lower temperatures. However, a liquid additive... 

This process is also called supercritical fluid antisolvent (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 liquid 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. 

The bottom-up technique refers to synthesis based on atom-by-atom or molecule-by-molecule arrangement in a controlled manner, which is regulated by thermodynamic means (Keck et al. 2008). The process takes place through controlled chemical reactions, either gas or liquid phase, resulting in nucleatiOT and growth of nanoparticles. Bottom-up techniques (like supercritical fluid antisolvent techniques, precipitation methods etc.) create heavily clustered masses of particles that do not break up on reconstitution (Shrivastava 2008 Mishra et al. 2010). 

Carpet Waste Using a Supercritical Fluid Antisolvent Technique , Polymer-Plastics Technology and Engineering, Vol.38, No. 3,411—432. 

Supercritical fluids can be used to induce phase separation. Addition of a light SCF to a polymer solvent solution was found to decrease the lower critical solution temperature for phase separation, in some cases by mote than 100°C (1,94). The potential to fractionate polyethylene (95) or accomplish a fractional crystallization (21), both induced by the addition of a supercritical antisolvent, has been proposed. In the latter technique, existence of a pressure eutectic ridge was described, similar to a temperature eutectic trough in a temperature-cooled crystallization. 

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). 

Depolymerization, e.g., polyethylene terephthalate and cellulose hydrolysis Hydrothermal oxidation of organic wastes in water Crystallization, particle formation, and coatings Antisolvent crystallization, rapid expansion from supercritical fluid solution (RESS)... 

Reverchon, E. (1999) Supercritical antisolvent precipitation of micro- and nano-particles. Journal of Supercritical Fluids, 15 (1), 1-21. 

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. 

Jarmer DJ, Lengsfeld CS, Randolph TW. 2006. Scale-up criteria for an injector with a confined mixing chamber during precipitation with a compressed fluid antisolvent. J. Supercritical Fluids 37 242-253. 

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... 

The supercritical fluid mefhod is a relafively new method, which can minimize the use of organic solvents and harsh manufacturing conditions taking advantage of two distinctive properties of supercritical fluids (i.e., high compressibility and liquid-like density). This method can be broadly divided into two parts rapid expansion of supercritical solutions (RESS), which utilizes the supercritical fluid (e.g., carbon dioxide) as a solvent for the polymer, " and supercritical antisolvent crystallization (SAS), using the fluid as an antisolvent that causes polymer precipitation. Recent reviews of the supercritical technology for particle production are available in the literature. ... 

Jarmer, D.J. Lengsfeld, C.S. Randolph, T.W. Manipulation of particle size distribution of poly(-lactic acid) nanoparticles with a jet-swirl nozzle during precipitation with a compressed antisolvent. J. Supercrit. Fluids 2003, 27 (3), 317-336. 

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. 

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