ASES Aerosol Solvent Extraction

Recently, Bustami et al. have investigated the feasibility of the ASES (aerosol solvent extraction system) process to generate microparticles of proteins for inhalation. Protein powders generated were of particle size 100nm-500nm. In vitro performance showed 65, 40, and 20wt.% respirable fraction for lysozyme, albumin, and insulin, respectively. Little or no loss of monomer content was observed for these proteins. 

ASES Aerosol solvent extraction system involves spraying of a polar liquid with a substrate as fine droplets into an atmosphere of compressed carbon dioxide causing precipitation of fine nanoparticles... 

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). 

Abbreviations ASES, aerosol solvent extraction system BSA, bovine serum albumin PCA, precipitation with compressed antisolvent PLA, polylactic acid PLGA poly(lactic-co-glycolic acid) PMMA, poly(methyl methacrylate) PPG, poly(propylene glycol) RESS, rapid expansion of supercritical solution TFE, 2,2,2-trifluoroethanol. 

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). 

Currently, there exist numerous antisolvent processes based on SCF CO2. These include, in alphabetical order, ASES (aerosol solvent extraction system) (70), GAS (gas antisolvent) (71), PCA (precipitation using a compressed antisolvent) (72), SAS (supercritical antisolvent) (67), SAS-EM... 

ASES (aerosol solvent extraction system) This is the first modification of the gas antisolvent process and involves spraying the solution through an atomization nozzle as fine droplets into compressed carbon dioxide (Figure 8.4). The dissolution of the SCF into the liquid droplets is accompanied by a large volume expansion and, consequently. 

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. 

ASES aerosol solvent extraction system, GAS gas antisolvent precipitation, PGSS precipitation from gas-saturated solutions, RESS Rapid expansion of supercritical solutions, SAS supercritical... 

In the second method the solution is sprayed through a nozzle into compressed carbon dioxide the process is termed as precipitation with compressed antisolvent (PCA) [33] and liquid or supercritical antisolvents can be employed. In the case of continuous flow of the solution and of the antisolvent the process is termed also as aerosol solvent extraction system (ASES) [34], in the case of countercurrent flow and supercritical antisolvent precipitation (SAS) in the case of co-current flow [35]. 

Aerosol Solvent Extraction System (ASES) Here, the solution is sprayed through atomization nozzle into a chamber L lied with SCF. Expansion of solution occurs within the Lne droplets of solvent being sprayed, thus creating supersaturation and precipitation of solids as Lne particles. 

Several processes utilizing supercritical fluids for materials processing have been reported in the literature although their commercial use is not well documented. Among the well-known processes are rapid expansion of supercritical solutions (RESS) (Phillips and Stella, 1993), the gas antisolvent process (GAS) (Yeo et al., 1993), aerosol solvent extraction system (ASES) (Bleich and Muller, 1996), a precipitation with compressed antisolvent process (PCA) (Brennecke, 1996), and solution-enhanced dispersion by supercritical fluids (SEDS) (Samp et al., 2000). The first four processes are for products that are soluble in the supercritical fluid or in an organic solvent. Biomolecules such as proteins or nucleic acids cannot be dissolved, and for such processes... 

SCE-based processes such as GAS process, SAS process, aerosol solvent extraction system (ASES), SEDS address low solubility of the compounds in SCCO2. In these processes, the drug, polymer, or both are dissolved in an organic solvent to form a solution. Solvents used may include dimethyl sulfoxide, N-methyl pyrrolidone, methanol, ethanol, acetone, chloroform, or isopropanol. To successfully produce ASD, the drug and polymer should exhibit limited solubility in SCF and the organic solvent should be miscible with carbon dioxide. Collection of the precipitated particles in the antisolvent is carried out in the same vessel where solvent extraction takes place. The particles are collected on a filter unit located at the bottom of the vessel. 

Some organic solvents, for example isobutyl methyl ketone (4-methylpen-tan-2-one) and ethyl acetate, produce particularly fine aerosol and very high transport efficiency as a consequence.8 Such solvents are therefore particularly useful for solvent extraction where very low detection limits are required. 

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. 

The importance of particle sizing is that only small particles will reach the lung, since the nose and mouth will remove any larger particles. There is continuing debate as to what maximum size will reach the lung, but consensus is for around 5 to 7 um. For alveoli penetration, a size of 3 lam is required, but very fine particles, below 1 jun, may be exhaled. It is the size of the droplets in the aerosol cloud that is important for dry powders and fully evaporated liquid suspensions, this maybe the original powder particle. Hence, it is essential to have powders in the micron range, and normal micronisation will usually produce a size of 1 to 3 jun. Newer techniques, such as supercritical fluid extraction, can produce smaller particles. Naturally, if the product is a solution, the particle size formed on evaporation of the solvent will depend on solution concentration. 

Solvent extraction combined with chromatographic techniques generally is used to study organic compounds associated with the atmospheric aerosol. Combustion to C02 is additionally used to determine total organic carbon in the samples. This includes elemental carbon present as soot. Due to the limited efficiency of solvent extraction and because many compounds show-... 

Demeon D Dimethyl ether DME Dymel A EINECS 204-065-8 Ether, dimethyl Ether, methyl HSDB 354 Methane, oxybis- Methoxymethane Methyl ether Methyl oxide Oxybismethane UN1033 Wood ether. Used as a solvent, motor fuel and Aerosol propellant, in refrigerants, as an extraction agent, a catalyst and stabilizer in polymerization. Gas mp = -141.5° bp = -24,8° Xm = 163,184 nm (s = 3981, 2512, gas) slightly soluble in CeHe, soluble in H20, EtOH, Et20, Me2CO. 

Methylene chloride is a volatile, colorless, nonflammable liquid. It is slightly soluble in water and miscible with many other solvents, such as acetone, chloroform, carbon tetrachloride, and alcohol. Under speciflc conditions it may burn. Its commercial formulations for paint stripping are particularly flammable. Methylene chloride is a widely used solvent where quick drying (i.e., high volatility) is required. Such application areas include adhesives, cellulose acetate flber production, blowing of polyurethane foams, and metal and textile treatment. It dissolves oils, fats, waxes, many plastics, bitumen, and rubber. This property is used in paint stripper formulations. It is used as an aerosol solvent, and for extraction operations in the pharmaceutical industry. It was previously used in fire-extinguishing products. ... 

OTHER COMMENTS used as a solvent for fats, waxes, synthetic resins, tar and alkaloids used as a solvent for adhesives, and extraction solvent, and as a solvent in textile dyeing acts as both a vapor pressure depressant, and as a solvent and carrier for many of the active ingredients used in aerosols used in vapor and metal degreasing... 

Isopropyl alcohol is extensively used in cosmetics, particularly for hair and skin lotions, and in pharmacy for preparations intended for external use. A further large area of use is the paint and printing ink industry. Isopropyl alcohol is added to fuels to prevent the icing up of the carburetor and increase the octane number. It is an important feedstock for the chemical industry, for example, in the production of acetone (particularly in the United States), esters, plasticizers, and ethers. Isopropyl alcohol is also important as a solvent (e.g., for recrystallization and extraction) and as a moistening agent for cellulose nitrate. It is furthermore used in the aerosol sector. 

Methylal [109-87-5] (formaldehyde dimethyl acetal, dimethoxymethane) is a pleasantly smelling, extremely volatile solvent. It dissolves polystyrene, polyfvinyl acetate), vinyl chloride copolymers, acrylates, methacrylates, and synthetic and natural resins. It is used in paints and lacquers, adhesives, and aerosols. Important extracting agent for natural substances, essences, and oils. It serves as a reaction medium in the chemical industry and as an intermediate for chemical syntheses. 

Brinker and coworkers also prepared photoresponsive nanoporous silica particles using aerosol-assisted assembly, EISA, and surfactant-directed self-assembly (SDSA) techniques (Liu, 2004). The as-prepared photoresponsive nanocomposite particles were prepared so that the azobenzene ligands pointed toward the hydrophobic micellar interiors. After surfactant removal by solvent extraction, nanoporous particles with azobenzene ligands positioned on the pore surfaces were formed (Fig. 13.8). 

The size exclusion method was initially performed using DVB 100 A column for quantitation of KHI hy using refractive index (RID) and Corona Aerosol Detectors (CAD). The eluent used is an HPLC grade Tetrahydrofiiran (THF). Chloroform is selected as a solvent to prepare the standards and to extract the samples. The chromatography is conducted at ambient temperature with ImL /min flow rate. The injection volume of the sample is 100 pL. The standards are prepared at a concentration... 

Dimethyl ether is used as a solvent in aerosol formulations. Diethyl ether as a commercial product is available in several grades and is used as an extraction solvent, reaction solvent, and as a general anesthetic. Ethyl ether is an excellent solvent for alkaloids, dyes, fats, gums, oils, resins, and waxes. Blends of ethyl ether and ethanol are excellent solvents for cellulose nitrate used in the manufacture of guncotton, in collodion solutions and pyroxylin plastics. Ethyl ether is used in the recovery of acetic acid from aqueous solutions in the cellulose acetate and plastic industry. It is used as a starter fuel for diesel engines and as a denaturant in denatured ethanol formulations. Grignard and Wurtz-Fillig synthesis reactions use diethyl ether as an anhydrous, inert reaction medium. 

A major problem in the treatment of nonaqueous systems is the removal of eolloidal particles to produce acceptable liquid products (e.g., fuel oil). Such a situation is encountered in hydrocarbon production from tar sands and oil shale. The particles (such as oxides, silicates, and clay mineral) suspended in the hydrocarbon hquids originate from a rock matrix. Particle separation problems occur in the solvent extraction of bitumen with nonaqueous media such as toluene. Electrostatic forces (bonding forces) play a predominant role in the physical state of these nonaqueous systems. In many instances, by addition of antisolvents, and selecting the proper temperature and agitation, these systems can be altered to improve solid separation. Separation of carbon black particles suspended in tetralin using Aerosol OT as a surfactant and by filtration through a bed of sand (deep-bed filtration) is another example of liquid-solids separation in nonaqueous systems. 

Dichloromethane is used as a cleaning agent (e.g. in electronics) and paint remover (45 - 50 %), in aerosol formulations (20 - 25 %), as extracting agent for decaffeinating of coffee, extracting of hops, paraffin extraction, and as a solvent. 

---