Precipitation with compressed fluid

D.J. Dixon, K.P. Johnston, R. Bodmeier, Polymeric materials formed by precipitation with compressed fluid antisolvent, A/Ch 7,39(1), 127-139,1993. 

Micronization with supercritical fluids - Crystallization - Rapid expansion - Gas anti-solvent Recrystallization - Precipitation with compressed anti-solvent - Solution-enhanced dispersion - Particles from gas-saturated solutions 80 - 300 fine particles and powders from various products and of designed properties... 

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). 

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... 

There have been several reviews of RESS over the past decade, with the most comprehensive being the 1991 work of Tom and Debenedetti (7), as it discusses both theory and experimental work in detail. An updated review of their modeling work was presented 2 years later (8). In more recent years, reviews have become more general, discussing RESS as one of several alternatives for processing materials with supercritical fluids (9-11). Such a development is, of course, not surprising, as many of the other techniques (such as supercritical antisolvent (SAS) and precipitation with compressed antisolvent (PCA) processes) have been developed to overcome one of the disadvantages of RESS, namely, the limited solubility of many materials in supercritical carbon dioxide. 

D. J. Dixon, "Formation of Polymeric Materials by Precipitation with a Compressed Fluid Antisolvent," Ph.D. Dissertation, University of Texas at Austin, Austin, Tex., 1992. 

PCA [Precipitation with a compressed anti-solvent] 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 microporous fibers. 

Dixon, D. J., Johnston, K. P. and Bodmeier, R. A. AIChE Jl. 39 (1993) 127. Polymeric materials formed by precipitation with a compressed fluid antisolvent. 

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. 

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. 

In the last ten years new, innovative processes utilizing supercritical fluids have received increasing attention. Here, we focus on two examples the Gas /IntLSolvent process (GAS) [1], also known as PC A (Precipitation with a Compressed fluid /Intisolvent) [2], and Supercritical /Intisolvent induced phase Separation (SAS)[3, 4],... 

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. 

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). 

PRECIPITATION WITH A COMPRESSED FLUID ANTISOLVENT (PCA), A SUPERCRITICAL ANTISOLVENT (SAS), AND THE AEROSOL SOLVENT EXTRACTION SYSTEM (ASES) PROCESSES... 

Dozens of drugs have been recrystallized by means of the precipitation with a compressed fluid antisolvent (PCA) and the supercritical antisolvent (SAS) and aerosol solvent extraction system (ASES) processes. 

Mawson S, Kanakia S, Johnston KP. Coaxial nozzle for control of particle morphology in precipitation with a compressed fluid antisolvent. J Appl Poly Sci 1997 64 2105-2118. 

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. 

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