title: Degradation Kinetics and Mechanism of a β-Lactam Antibiotic Intermediate, 6-Aminopenicillanic Acid, in a New Integrated Production Process.
abstract: In an effort to promote sustainability and to reduce manufacturing costs, the traditional production process for 6-aminopenicillanic acid (6-APA) has been modified to include less processing units. The objectives of this study are to investigate the degradation kinetics of 6-APA, to propose a reasonable degradation mechanism, and to optimize the manufacturing conditions within this new process. A series of degradation kinetic studies were conducted in the presence of impurities, as well as at various chemical and physical conditions. The concentrations of 6-APA were determined by high-performance liquid chromatography. An Arrhenius-type kinetic model was established to give a more accurate prediction on the degradation rates of 6-APA. A hydrolysis degradation mechanism is shown to be the major pathway for 6-APA. The degradation mechanisms and the kinetic models for 6-APA in the new system enable the design of a good manufacturing process with optimized parameters.
authors: School of Marine Science and Engineering, Hebei University of Technology, Tianjin 300130, China; State Research Center of Industrialization for Crystallization Technology, School of Chemical Engineering and technology, Tianjin University, Tianjin 300072, China; School of Chemical Engineering, Hebei University of Technology, Tianjin 300130, China. Electronic address: sumin@tju.edu.cn.
authors: Min
authors: M
authors: Su
authors: College of Chemical and Pharmaceutical Engineering, Hebei Universtity of Science and Technology, Shijiazhuang 050018, China; State Research Center of Industrialization for Crystallization Technology, School of Chemical Engineering and technology, Tianjin University, Tianjin 300072, China.
authors: Hua
authors: H
authors: Sun
authors: School of Marine Science and Engineering, Hebei University of Technology, Tianjin 300130, China; State Research Center of Industrialization for Crystallization Technology, School of Chemical Engineering and technology, Tianjin University, Tianjin 300072, China.
authors: Yingying
authors: Y
authors: Zhao
authors: School of Marine Science and Engineering, Hebei University of Technology, Tianjin 300130, China.
authors: Aidang
authors: A
authors: Lu
authors: School of Chemical Engineering, Hebei University of Technology, Tianjin 300130, China.
authors: Xiaohui
authors: X
authors: Cao
authors: State Research Center of Industrialization for Crystallization Technology, School of Chemical Engineering and technology, Tianjin University, Tianjin 300072, China.
authors: Jingkang
authors: J
authors: Wang
mesh_terms: D000900:Anti-Bacterial Agents / Q000032:analysis / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination / Q000517:prevention & control*; D004355:Drug Stability; D006868:Hydrolysis; D007700:Kinetics; D008956:Models, Chemical; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry; D012996:Solutions; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature
chemical_list: D000900:Anti-Bacterial Agents; D012996:Solutions; D010397:Penicillanic Acid; C004408:aminopenicillanic acid
keywords: chemical stability; degradation products; kinetics; processing; unit operations