The influence of operating conditions on the dense gas precipitation of model proteins

Dense gas techniques provide a suite of clean technology options for the pr ocessing of pharmaceuticals. Monodisperse, micron-sized particles can be pr oduced at mild operating temperatures and with negligible solvent residue. In this study, protein was precipitated from organic solutions using dense carbon dioxide as antisolvent. The gas antisolvent precipitation process (G AS) was used to produce biologically active lysozyme, insulin, and myoglobi n powders. The effects of operating temperature, solute concentration and t he rate of antisolvent addition on the morphology, size, activity and resid ual solvent concentration of lysozyme and insulin precipitates have been ex amined. The powders produced consisted of uniformly sized non-aggregated sp herical particles. Precipitate size was controlled between 0.05 mu m and 2. 0 mu m by changes to the solvent and antisolvent compositions. In general t he concentration of residual organic solvent was found to be dependent on t he mass of antisolvent used during the washing cycle. Residual concentratio ns as low as 300 ppm were easily achievable in a single step. (C) 2000 Soci ety of Chemical Industry.