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Pharmaceuticals and Supercritical Fluid ApplicationsSome compounds, particularly pharmaceuticals, are difficult to micronize by conventional grinding or jet milling. For example, materials that have low (< 60°C) melting point or that are waxy cannot be ground or milled to fine size (< 1 or 2 m) because they will smear or form amorphous (and size unstable) particles. Two supercritical fluid processes have been developed in response to these difficulties. In one, supercritical fluids are employed to dissolve a compound, then by pressure decrease cause precipitation, and in the other the gas acts as an antisolvent, causing recrystallization because of solubility decrease. The pressure dependent solubility of materials in SCFs forms the basis of the particle formation process termed RESS (Rapid Expansion of Supercritical Solutions); RESS is employed with SCF soluble compounds. If a compound is not soluble in a gas (and many very polar compounds are not), the gas can be used as an antisolvent, causing recrystallization when the gas and an organic solvent solution are admixed. The process termed GAS (Gas Anti Solvent) Recrystallization exploits the miscibility of carbon dioxide with virtually all laboratory and industrial solvents. With a gas antisolvent the rapidity and intimacy of mixing far exceeds what liquid antisolvents can achieve. SCF recrystallization processes have been applied to scores of pharmaceuticals, polymers, cosmetics, biomolecules, dyes, and even explosives. The advantages of both processes reside in the, literally, millisecond time scale for pressure reduction or admixing of solution and gas, which creates a high supersaturation ratio resulting in the formation of ultrafine particles of narrow size range. The ability to produce micron or submicron particles opens up a spectrum of opportunities for the creation of new or improved products. For example, creation of a new pharmaceutical product that could be delivered via inhalation instead of parenterally, would certainly justify the application of supercritical fluids, especially if traditional jet milling could not achieve the desired product characteristics. Reducing the particle size of a steroid. The jet milled steroid shown below in the top photograph contains 8%
particles larger than 3 microns, and it cannot be used in a specific ophthalmalogical
ointment. Current particle processes are inadequate for producing the
required particle size and size distribution to meet the stringent specification:
no particles greater than 3 microns.
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