Supercritical fluid nucleation

Instead of discussing the most recent work then progressing to material from the first edition, we start with the older material then progress to the new. Our first topic is supercritical fluid nucleation. 

The first reports of solubility phenomena in supercritical fluids emphasized the pressure-dependent dissolution characteristics of high-pressure gases and liquids. But the authors of those early papers point out the potential application of using SCF solvents as media from which to nucleate solid materials. For example, Hannay and Hogarth write in the closing statements of their 1879 publication  

We have, then, the phenomenon of a solid with no measurable gaseous pressure, dissolving in a gas. When the solid is precipitated by suddenly reducing the pressure, it is crystalline, and may be brought down as a snow in the gas, or on the glass as a frost, but it is always easily redissolved by the gas on increasing the 

The snow and frost described are almost assuredly of different morphology, particle size, and size distribution than the starting material Hannay and Hogarth studied salts such as cobalt chloride and potassium iodide. Incidentally, the reference to the precipitation of the solid is not an Isolated report of nucleation from a supercritical fluid. For example, many other references to snow, fog, fumes, and crystals formed during depressurization of a solution of a solute in a supercritical fluid have been made by researchers studying supercritical fluid solubility phenomena. 

The particle size and size distribution of solid materials formed in industrial processes is frequently not desired for subsequent reaction or use of 

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Coffey, M. P., Krukonls, V. J. Supercritical Fluid Nucleation An Improved Ultra-Fine Particle Formation Froc sa. Phasex Corp. Final Report to National Science Foundation 1988, Contr. ISI-8660823. 

Krukonls. V.. "Supercritical Fluid Nucleation of Difficult to Comminute Solids." presented at the AIChE Annual Meeting. San Fransisco. 

Sievers RE, Hybertson B, Hausen B. European patent EP 0627910B1, 1993. Krukonis V. Supercritical fluid nucleation of difficult-to-comminute solids. Proceedings of the AIChE Meeting, San Francisco, 1984. 

Krukonis VJ. Supercritical fluid nucleation of diflicult-to-comminute solids. Annual Meeting, American Institute of Chemical Engineers Journal, San Francisco, November 1984 140-149. 

Coffey MP, Krukonis VJ. Supercritical Fluid Nucleation. An Improved Ultra-fine Particle Formation Process. Phasex Corp., Final report to the National Science Foundation, 1988. 

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 final example of SCF comminution is a comparison of polypropylene particles out of the bottle and after supercritical fluid nucleation. Instead of carbon dioxide, supercritical propylene at 241 bar (3,500 psia) and 140°C is used to dissolve the sample of polypropylene. Figure 12.5a is a high-magnification SEM of a single parent particle. As shown in figure 12.5b, a very different particle size and shape results from the supercritical fluid process. 

Many other papers on supercritical fluid nucleation later appeared in the literature. Larson and King (1986) studied the nucleation of various pharmaceuticals. Smith and coworkers, e.g., Matson, Peterson, and Smith (1986), reported on metal oxides, polymers, and other materials. Smith and coworkers... 

An extension of supercritical fluid nucleation to industrial operation is shown schematically in figure 12.8. In the supercritical fluid nucleation report to NSF, Coffey and Krukonis (1989) carried out economic viability analyses of the process. A solid material is charged to an extraction vessel and an appropriate gas, such as carbon dioxide, passed through the charge. The... 

Figure 12.8 Schematic diagram of supercritical fluid nucleation operated at commercial scale.

Not every pharmaceutical will eventually be comminuted by supercritical fluid nucleation, not every polymer processed for molecular weight control by supercritical fluid extraction, not every flavor concentrated by supercritical fluid extraction but some will be. Two applications listed in the table are already in commercial production, and several are in advanced pilot plant development and test market evaltiation. Hops extraction is being carried out by Pfizer, Inc. in its plant in Sydney, NE (33), and General Foods Corporation has constructed a coffee decaffeination... 

Krukonis V.J. 1984. Supercritical fluid nucleation of difficult to comminute sohds. Paper 104f presented at AIChE Meeting in San Francisco, California, November 1984. 

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