Pharmaceuticals | Uses for Supercritical Fluids

Supercritical Fluids in the Pharmaceutical Industry


Supercritical fluids can be applied in numerous pharmaceutical

areas including chromatography, drug discovery, and the

synthesis, purification and extraction of drug compounds.

In addition, many drug delivery applications provide increased

benefits compared with conventional techniques.


Supercritical CO2 is the most widely used supercritical fluid in the pharmaceutical industry because it has a low critical temperature (31°C), is non-flammable, non-toxic, inexpensive and is Generally Recognized as Safe (GRAS).




Flash chromatography    (see eCO2Chrom)

Flash chromatography using liquid organic solvents is the typical approach for small molecule purification in medicinal chemistry laboratories. Replacing nonpolar toxic solvents with liquid CO2 has been shown to be an attractive alternative to the flash LC technique. High loadings are possible using dry pack techniques with liquid CO2 flash chromatography. In addition, liquid CO2 flash chromatography has greatly reduced solvent usage and increased productivity due to better efficiencies seen at higher flow rates. Products isolated from flash liquid CO2 flash chromatography are approximately four times more concentrated than traditional LC flash fractions, reducing time required for isolation of dry product. Finally the use of the liquid CO2 flash technique significantly reduces the amount of toxic solvents utilized in medicinal chemistry laboratories.


Chiral chromatography    (see eCO2Chrom)

Using liquid CO2 as a mobile phase is an attractive alternative to HPLC for many chiral separations. For normal-phase separations, this liquid CO2 technique improves enantiomer resolution with higher efficiencies and faster separations with a substantial decrease in pressure drop across the chromatographic column.



Drug delivery


Nanoparticles          (see Nanoparticles)


Particle Coating

Sometimes coating of a drug compound is required to modify the release profile of the drug,  enhance its stability or improve handling of materials. Supercritical fluid technology is capable of replacing organic solvents in traditional methods. The coating is solubilized in supercritical CO2 and contacted with the drug powder in a apparatus similar to fluid bed dryer.


Amorphous Drug Preparation

Poorly soluble drugs and excipients can be made more soluble using various supercritical CO2 processes. Frequently an insoluble crystalline drug or excipient can be converted into a more soluble amorphous form under supercritical conditions.


Drug purification and extraction and infusion


Extraction removal of residual solvents

Carbon-dioxide extraction offers an attractive means to remove residual solvent from drugs and polymers contaminated with organic solvent residues.  Supercritical CO2 extraction is a quick, environmentally benign process that easily dissolves organic solvents and does not alter polymer chemistry or leave undesirable residues.


Impregnation/infusion of compounds into polymeric materials and medical devices


Supercritical carbon dioxide impregnation of a drug compound into polymeric materials or medical devices has the potential to eliminate the toxic organic solvents typically used in these processes. In addition, the concern of residual solvents remaining in the polymeric matrix or medical device is eliminated.  Supercritical fluids accelerate the diffusion of a pharmaceutical compound into a polymer compared to organic solvents.  After the rapid supercritical diffusion process, the supercritical fluid can be easily depressurized to entrap the pharmaceutical compounds in the void volume of a swollen polymeric matrix or medical device.






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