6060 Spine Road  Boulder CO 80301 303-350-3060  www.aktiv-dry.com

1. Drug solution or suspension Flow restrictor tube ID = 75 µm 10 cm Restrictor tip Plume CO2 flashes upon rapid 100X decompression to atmospheric pressure AKTIV-DRY The CAN-BD®* Process *Carbon dioxide Assisted Nebulization with a Bubble Dryer 6060 Spine Road  Boulder CO 80301 303-350-3060  www.aktiv-dry.com CAN-BD is Aktiv-Dry’s proprietary process for making fine, dry powders of pharmaceutical, biotech, and other compounds. The heart of CAN-BD is high pressure nebulization assisted by supercritical fluids, usually CO2, but N2 has also been used. Nebulization occurs when the supercritical, or near-critical, fluid mixes with a solution or suspension of the pharmaceutical product to form an emulsion that expands abruptly from 80 bar to atmospheric pressure through a capillary flow restrictor. Microbubbles that form during the expansion burst almost instantaneously at atmospheric pressure to create a plume of billions of nano-scale droplets. When the plume is directed into a drying chamber, not unlike that used in spray drying, the liquid solvent evaporates to leave behind fine particles that may be collected on filters, bags, or in cyclone separators. Particle size distributions may be engineered by changing process variables. CAN-BD has been used with aqueous and organic solvents and with nano-suspensions. Solutes have included proteins, peptides, live vaccines and many other compounds and excipients. Supercritical CO2 (80 to 100 atm) • Very narrow size distribution range • Drying takes place in seconds, not hours • Continuous process • Environmentally friendly - Uses CO2 and water for most applications • Compatible with organics • No toxic residues or waste to create disposal problems • Lower temperatures minimize decomposition of thermally liable materials such as certain drugs and proteins CAN-BD is capable of making particles for virtually any application, including dry pharmaceutical powders for pulmonary drug delivery