Dry powders of stable protein formulations from aqueous solutions preparedusing supercritical CO2-assisted aerosolization

We report on the use of a new supercritical carbon dioxide-assisted aerosol ization coupled with bubble drying technology to prepare stabilized, dry, f inely divided powders from aqueous protein formulations. In this study, the feasibility of this new technology was tested using two model proteins, ly sozyme and lactate dehydrogenase (LDH). In the absence of excipients, lysoz yme was observed to undergo perturbations of secondary structure observed b y solid-state infrared spectroscopy. In the presence of sucrose, this unfol ding was minimized. Lysozyme did not, however, undergo irreversible loss of activity, as all lysozyme powders generated by supercritical CO2-assisted aerosolization (with or without excipients) regained almost complete activi ty on reconstitution. The more labile LDH suffered irrecoverable loss of ac tivity on reconstituting after supercritical CO2-assisted aerosolization an d bubble drying in the absence of carbohydrate stabilizers. LDH could be st abilized throughout the nebulization, drying, and rehydration processes wit h the addition of sucrose, and almost complete preservation of activity was achieved with the further addition of a surface active agent, such as Twee n 20, to the aqueous formulation prior to processing. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:785-797, 20 01.