PROCESS DEVELOPMENT AND CASE STUDIES OF CONTINUOUS REACTOR SYSTEMS FOR PRODUCTION OF API AND PHARMACEUTICAL INTERMEDIATES

This chapter discusses opportunities for continuous processing of pharmaceutical intermediates and active pharmaceutical ingredients, and reviews some considerations for developing and implementing continuous processes. The three main components of a continuous reaction process include the feed solutions, the reactor, and the quench. The chapter first considers the reactor followed by the ancillary systems for the feed solutions and quench. The quench brings the reaction mixture to a nonreactive and stable condition for downstream processing. The quench can be chemical or thermal in nature, and the choice depends on the reactivity of the processing stream and downstream processing needs. The chapter also presents two brief case studies from the authors' experience, and considers some of the barriers to widespread use of continuous processes. Continuous operation may not be appropriate for all processes. When looking for development opportunities, the initial focus should be on processes that have safety issues, followed by issues of quality, and lastly economics.