title: Solvent removal and spore inactivation directly in dispensing vials with supercritical carbon dioxide and sterilant.
abstract: A process is described using supercritical carbon dioxide to extract organic solvents from drug solutions contained in 30-mL serum vials. We report drying times of less than 1 h with quantitative recovery of sterile drug. A six-log reduction of three spore types used as biological indicators is achieved with direct addition of peracetic acid to a final concentration of approximately 5 mM (~0.04 %) to the drug solution in the vial. Analysis of two drugs, acetaminophen and paclitaxel, indicated no drug degradation as a result of the treatment. Furthermore, analysis of the processed drug substance showed that no residual peracetic acid could be detected in the final product. We have demonstrated an effective means to simultaneously dry and sterilize active pharmaceutical ingredients from organic solvents directly in a dispensing container.
authors.affiliation: CritiTech, Inc, 1321 Wakarusa Drive, Suite 2102, Lawrence, Kansas 66049, USA.
authors.forename: Jahna
authors.initials: J
authors.lastname: Howell
authors.forename: Fengui
authors.initials: F
authors.lastname: Niu
authors.forename: Shannon E
authors.initials: SE
authors.lastname: McCabe
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Decedue
mesh_terms: D000082:Acetaminophen / Q000737:chemistry; D001407:Bacillus / Q000502:physiology; D002245:Carbon Dioxide / Q000737:chemistry*; D011232:Chemical Precipitation; D002851:Chromatography, High Pressure Liquid; D025924:Chromatography, Supercritical Fluid; D004340:Drug Contamination / Q000517:prevention & control*; D004349:Drug Packaging; D004355:Drug Stability; D004866:Equipment Contamination / Q000517:prevention & control*; D001411:Geobacillus stearothermophilus / Q000502:physiology; D010084:Oxidation-Reduction; D017239:Paclitaxel / Q000737:chemistry; D010463:Peracetic Acid / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry*; D013171:Spores, Bacterial; D013242:Sterilization / Q000379:methods*; D013678:Technology, Pharmaceutical / Q000379:methods*; D014465:Ultrasonics
chemical_list: D012997:Solvents; D002245:Carbon Dioxide; D000082:Acetaminophen; D010463:Peracetic Acid; D017239:Paclitaxel