Solution enhanced dispersion supercritical fluid process

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. 

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). 

One variant of the GAS or SAS process (SCF as antisoivent) is solution enhanced dispersion by supercritical fluids (SEDS). Coaxial nozzles are used to introduce drug solution and carbon dioxide at the desired temperature and pressure. In this case, the SCF carries out both droplet breakup and antisoivent functions. SEDS has been tested for a number of pharmaceutical compounds. As noted above, this is a continuing effort. 

SOLUTION-ENHANCED DISPERSION BY SUPERCRITICAL FLUIDS (SEDS) PROCESS... 

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. 

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). 

SEDS (solution-enhanced dispersion by supercritical fluids) The second modification of the gas antisolvent process known as solution-enhanced dispersion by SCFs was developed by the Bradford Universityt in order to achieve smaller droplet size and intense mixing of SCF and solution for increased transfer rates. Indeed the SCF is used both for its chemical properties and as spray enhancer by mechanical effect a nozzle with two coaxial passages allows the introduction of the SCF and a solution of active substance(s) into the particle-formation vessel where pressure and temperature are controlled (Figure 8.5). The high velocity of the SCF allows breaking up the solution into very small droplets. Moreover, the conditions are set up so that the SCF can extract the solvent from the solution at the same time as it meets and disperses the solution. Similarly, a variant was recently disclosed by the University of Kansas, where the nozzle design leads to development of sonic waves leading to very tiny particles, around 1 /rm. 

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... 

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. 

Solution-Enhanced Dispersion by Supercritical Fluid (SEDS) Process... 

Figure 3 (a) Schematic flow diagram of the solution-enhanced dispersion by supercritical fluids (SEDS) process, (b) Nozzle configurations of the SEDS and the precipitation by compressed antisolvent (PCA) processes. 

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. 

Dias et al., [119] developed dressings by impregnation of the antiinflammatory quercetin and anesthetic thymol by supercritical fluid in biopolymers Chen et al., [120] obtained micronized polymer composites loaded with lysozyme by the process of solution-enhanced dispersion by supercritical CO2 from a solution containing lysozyme / poly (L-lactide) / poly (ethylene glycol). Morgado et al., [121] successfully used supercritical CO2 for... 

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