Micronization of water-soluble or alcohol-soluble pharmaceuticals and model compounds with a low-temperature Bubble Dryer®

Carbon dioxide assisted nebulization with a Bubble Dryer® (CAN-BD) can dry and micronize pharmaceuticals for pulmonary drug delivery [1–11]. In this process, the drug, dissolved in water or an alcohol (or both), is mixed intimately with near-critical or supercritical CO2 by pumping both fluids through a low volume tee to generate microbubbles and microdroplets, which are then decompressed into a low temperature drying chamber, where the aerosol plume dries in seconds. CO2 and the solution are mixed in the tee at room temperature and microbubbles and microdroplets formed are dried rapidly at lower temperatures (25–80 °C) than are used in traditional spray drying processes. The residence time of the particles in the lab scale 750 ml glass drying chamber is less than 3 s. The primary advantage of this process is that there is less decomposition of thermally labile drugs. Secondly, no high-pressure vessels are needed in the CAN-BD process, except for the syringe pump, the 1/16 inch OD stainless steel tubing, the low volume tee, and the flow restrictor, which allow fluid mixing at a moderate pressure (i.e. between 80 and 100 bar) and the expansion of the microbubbles and microdroplets to atmospheric pressure. Thirdly, these particles (hollow or solid) are generally formed in the optimum size range for pulmonary delivery to alveoli (typically 99% are less than 3 μm in diameter). We have synthesized and measured the aerodynamic diameters of dried hollow and solid particles of various drugs and model compounds. Particles can be easily prepared and collected in a CAN-BD unit. Samples as small as 1 ml in volume can be dried for formulation studies, and scale-up of the CAN-BD process is in progress.