Eiffel's Toolbox of Supercritical Fluid (SCF) Technologies

Eiffel's Supercritical Fluid (SCF), or “dense gas” technologies are used to produce very small particles of therapeutic agents. The powders produced typically have very small particle size range distributions and consistent surface properties, which are difficult to achieve by conventional techniques.

These outcomes are made possible because of the unique properties of SCFs, where compounds display both liquid and gas-like properties under defined conditions of temperature and pressure. A SCF displays the solvent strength of a liquid, yet permeability similar to that of a gas. Carbon dioxide is most commonly used as the SCF, though other gases may also be used.

These properties form the basis of Eiffel’s engineering solution to the challenge of producing drug powders with physical properties that enhance their clinical and market performance.

Eiffel has the flexibility to apply the fundamental science in a range of methodologies for particle re-engineering. A SCF may be used as either a solvent or an anti-solvent, in various engineering process formats to cater for drugs with different chemistries in developing products with specific target performance characteristics.

Thre key methodologies (ASES, GAS, RESS) are described below, though other “hybrid” methods may also be developed in response to specific product requirements.

ASES - Aerosol Solvent Extraction System A bulk drug solution is sprayed into the dense gas environment. The droplets of drug solution expand rapidly, resulting in rapid precipitation as the drug passes from a solvent environment to an anti-solvent environment in a very short period of time. Applications and Advantages   The ASES process can be applied to the re-engineering of pharmaceutical compounds where the compound has very low solubility in the dense gas. ASES leads to extremely rapid continuous precipitation. An advantage of ASES is the rapid and continual extraction of solvent from the drug particles, enabling controlled particle growth, resulting in narrow particle size range distributions.
GAS - Gas Anti-Solvent System In the GAS process, the dense gas is added to the bulk drug solution and acts as an anti-solvent. With increasing gas concentration, the liquid phase expands and its ability to retain the drug in solution decreases. At a threshold expanded volume, the solution is saturated. Further addition of dense gas leads to supersaturation, causing the drug to precipitate. Continued addition of dense gas enables the maintenance of conditions close to supersaturation as the drug transfers from the dissolved state to the solid state. The solid product may be collected by filtration. Applications and Advantages   The GAS process can be applied in the re-engineering of pharmaceutical compounds where the compound has very low solubility in the dense gas. An advantage of the GAS process is that the rate of pressurization can be tightly controlled, leading to a high level of control over the rate of crystallisation and particle characteristics.
RESS - Rapid Expansion of Supercritical Solutions Particles are dissolved in a supercritical fluid which is then rapidly expanded into a low temperature and pressure environment. The sudden change in conditions causes rapid crystallization of the solute as micronised particles of a narrow size range. The solid product may be collected by filtration. Applications and Advantages   The RESS process can be applied to the re-engineering of pharmaceutical compounds where the compound has sufficient solubility in the dense gas. The main advantages of the RESS process are the absence of organic solvents and its simplicity for engineering development and scale-up.

Some Relevant Publications

Generation of Micro-Particles of Proteins for Aerosol Delivery Using Hugh Pressure Modified Carbon Dioxide
Rana T. Bustami, Hak-Kim Chan, Fariba Dehghani, and Neil R. Foster. Pharmaceutical Research, 2000, Vol. 17, No.11:1360 - 1366.

Synthesis, Purification, and Micronization of Pharmaceuticals Using the Gas Antisolvent Technique
B. Warwick, F. Dehghani, Neil R. Foster, J. R. Biffin and Hub L. Regtop. Industrial Engineering and Chemical Research, 2000, 39, 4571-4579.

Micronisation by Rapid Expansion of Supercritical Solutions to Enhance the Dissolution Rate of Poorly Water-Soluble Pharmaceuticals
M. Chareonchaitrakool, F. Dehghani, Neil R. Foster and H. K. Chan. Industrial Engineering and Chemical Research, 2000, 39, 4794-4802.

The Influence of operating conditions on the dense gas precipitation of model proteins
Russell Thiering, Fariba Dehghani, Angela Dillow and Neil R. Foster. Journal of Chemical Technology and Biotechnology, 2000, 75, 29-41.

Solvent effects on the controlled dense gas precipitation of model proteins
Russell Thiering, Fariba Dehghani, Angela Dillow and Neil R. Foster. Journal of Chemical Technology and Biotechnology, 2000, 75, 42-53.

Bacterial inactivation by using near- and supercritical carbon dioxide
Angela K. Dillow, Fariba Dehghani, Jeffrey S. Hrkach, Neil R. Foster, and Robert Langer.
Proceedings of the National Academy of Sciences of the United States of America., Aug 1999, 96, 10344-10348.

Dehghani, F. and Foster, N.R., “Dense Gas Anti-solvent Processes for Pharmaceutical Formulation”, Current Opinion in Solid State and Materials Science, 2003, 7(4-5), 363-369.

Foster, Neil; Mammucari, Raffaella; Dehghani, Fariba; Barrett, Angela; Bezanehtak, Keivan; Coen, Emma; Combes, Gary; Meure, Louise; Ng, Aaron; Regtop, Hubert L.; Tandya, Andrian. Processing Pharmaceutical Compounds Using Dense Gas Technology. Industrial & Engineering Chemistry Research 2003, 42 (25), 6476-6493

Research Team Publications

Publications (PDF, 60KB)

 

Page updated April 24, 2007