Continuous reactive crystallization of pharmaceuticals using impinging jet mixers

Abstract

For reactive crystallization of pharmaceuticals that show a rapid reaction rate, low solubility of active pharmaceutical ingredient and hence a large supersaturation, it was found in a recent study that a process design which integrates an impinging jet mixer and batch stirred tank produces high quality crystals. The current investigation examines if the short processing time of reactive crystallization permits the impinging jet mixer—stirred tank design to be modified to operate in a continuous mode. The new design combines an impinging jet mixer for feed introduction and reaction with a continuous stirred tank reactor (CSTR) and tubular reactor for crystal growth. A study of reactive crystallization of sodium cefuroxime (an antibiotic), using first a 1L CSTR then scaling to a 50L CSTR, found that the new design produces crystals of higher crystallinity, narrower particle size, and improved product stability, than batch crystallizers. © 2016 American Institute of Chemical Engineers AIChE J, 63: 967–974, 2017