SAS Supercritical Anti-Solvent

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. 

B. SAS — Supercritical Anti-Solvent Precipitation and Related Processes. 647... 

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. 

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

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)... 

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). 

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. 

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... 

The routes to particle synthesis via supercritical fluids basically follow two paths. Rapid Expansion of Supercritical Solution (RESS) and Supercritical Anti-Solvent (SAS). The basic processing steps are outlined in Figure 21.18 and Figure 21.19, respectively. RESS involves homogenization of the particles raw material in the supercritical fluid followed by rapid expansion of the solution through an expansion device such as a nozzle. Depending on the nozzle design, time-temperature and time-pressure profiles, and whether one uses... 

Both the nucleation of supercritical anti-solvent bubbles in a polymer+organic solvent-rich phase in the supercritical anti-solvent process (SAS) (or, equivalently, precipitation with a compressed antisolvent PCA) (e.g., [76]) and the nucleation of bubbles of a dissolved supercritical fluid from a saturated and nozzle-expanded solution containing a solute to be precipitated, in the formation of particles from gas-saturated solutions (PGSS) [77] are bubble nucleation problems, to which the above ideas apply. In the latter case, the nucleation of bubbles occurs simultaneously with that of solid particles within the bulk supersaturated solution. 

Besides the supercritical fluid extraction (SFE) for preparation of medicines and materials processing, supercritical fluid technology involves processes such as supercritical anti-solvent (SAS), rapid expansion supercritical solutions (RESS), rapid expansion of a supercritical solution into a liquid solvent (RESOLV), supercritical assisted atomization (SAA), impregnation and solution enhanced dispersion by supercritical CO2 (SEDS) that involves the supercritical fluid in drug processing to drug delivery systems. 

Vitexin is also able to induee apoptosis and suppress tumor growth in cancer models of breast, prostate, liver, cervical [90] and colon [91]. Zu et al., [92] obtained via supercritical anti-solvent (SAS), vitexin micronized powder with an average size of 126 nm with higher dissolution rate compared to the improcessed vitexin. 

Stephanie Careno, Olivier Boutin, Elisabeth Badens, Drug recrystallization using supercritical anti-solvent (SAS) process with impinging jets Effect of process parameters. Journal of Crystal Growth 342 (2012), p. 34-41. 

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). 

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

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. 

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