NANOPARTICLE AND MICROPARTICLE GENERATION WITH SUPER- OR NEAR-CRITICAL CARBON DIOXIDE

摘要

Fine dry particles can be generated by a patented process, CO_2-Assisted Nebulization with a Bubble Dryer~(~R) (CAN-BD). These particles, with aerodynamic diameter range of 400 nm to 5 μm, are suitable for pulmonary drug delivery or other applications in which nanoparticles or microparticles are desired. To generate these particles, two fluid streams (super- or near-critical CO_2 and an aqueous or organic solution), driven by two separate pumps, are mixed intimately in a small volume tee at or near room temperature and a predetermined pressure (e.g., 1200 psig). The resultant mixture is expanded through a flow restrictor to atmospheric pressure to generate an aerosol, which is then dried at a temperature at or below 60℃ to produce fine dry powders. Lately, a newly configured CAN-BD system utilizing one pump to drive both fluids has been developed. The fluid flow rate of each stream can be controlled to a certain degree with check valves and needle valves to produce a stable dense aerosol plume. The dry powders generated by the one-pump CAN-BD have similar characteristics as those generated by the two-pump CAN-BD, and yet the latter is more versatile. The result of comparison between these two CAN-BD systems will be discussed, Fine dry particles of different solutes (e.g., proteins, sugars, water-soluble drugs, or organic solvent-soluble drugs, etc) suitable for pulmonary delivery have been micronized using the two-pump CAN-BD process [3 to 8]. A parametric study, utilizing the two-pump CAN-BD system and ethanolic solutions containing betamethasone 17, 21-dipropionate, has been conducted, The results of the study will be presented.