Development and Scale-Up of a Continuous Manufacturing Process for a Hydrazine Condensation Reaction
Ruiheng Zhu, R. Shailaja Reddy, Man Ding, Ming Xu, Chaoyi Deng, Sam Tadayon, Hui Li, Kristopher M. Depew, Benjamin S. Lane
Abstract
The development of a continuous manufacturing process for a hydrazine condensation reaction at high temperature is reported. This continuous process represents a safer approach to manufacture 3-phenyl-1H-pyrazol-5-amine at scale and exhibits better impurity control compared to a traditional batch process. A controlled crystallization allowed consistently low levels of residual hydrazine (<20 ppm) in isolated solids for further processing to final drug substance. The scalability and robustness of the continuous process was demonstrated at 3 kg scale with a throughput of 0.5 kg/h.
Topics & Concepts
Hydrazine (antidepressant)CondensationCrystallizationProcess engineeringProcess developmentMaterials scienceAmine gas treatingImpurityCondensation reactionProcess controlProcess (computing)ScalabilityContinuous productionResidualChemical engineeringCombinatorial chemistryChemistryOrganic chemistryComputer scienceCatalysisChromatographyEngineeringAlgorithmThermodynamicsPhysicsComposite materialOperating systemDatabaseInnovative Microfluidic and Catalytic Techniques InnovationProtein purification and stabilityCrystallization and Solubility Studies