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Pure Appl. Chem., 2001, Vol. 73, No. 8, pp. 1299-1303

Low-temperature manufacturing of fine pharmaceutical powders with supercritical fluid aerosolization in a Bubble Dryer®

R. E. Sievers1*, E. T. S. Huang1, J. A. Villa1, J. K. Kawamoto1, M. M. Evans1 and P. R. Brauer2

1 Department of Chemistry and Biochemistry, 215 UCB, University of Colorado, Boulder, CO 80309-0215, USA
2 Temco, Inc., 4616 Mingo Rd., Tulsa, OK 74117, USA

Abstract: Aerosols play an important role in thin film deposition, fine powder generation, and drug delivery. Green processes to form aerosols are needed to eliminate the use of toxic organic solvents and minimize the production of liquid wastes and the emission of halogenated and oxidant-forming organic compounds. We have developed a new patented process, Carbon Dioxide-Assisted Nebulization with a Bubble Dryer® (CAN-BD), that can generate a dense aerosol with small droplet and microbubble sizes that are dried to form particles less than 3 µm in diameter [1­9]. The process uses carbon dioxide as an aerosolization aid, and this permits drying at lower temperature than usually needed in conventional spray-drying. Intimate mixing of supercritical carbon dioxide with aqueous protein solutions causes the formation of microbubbles, which are rapidly dried in less than 5 s. The process is more environmentally benign than traditionally used methods, and is superior when thermally unstable materials are being processed. Fine-particle pharmaceutical powders can be rapidly and easily made by this new CAN-BD process, requiring less energy and eliminating residues of toxicologically or environmentally objectionable solvents. Manufacturing dry powders of pharmaceuticals for pulmonary drug delivery and increasing bioavailability are the purposes of developing and marketing the new Temco Bubble Dryer.