The coupling of in-flow reaction with continuous flow seedless tubular crystallization

Abstract

The direct coupling between a continuous flow-assisted acetylation reaction of salicylic acid and the subsequent crystallisation of aspirin in a continuous flow tubular reactor or nucleator is investigated. The design of the reactor relies on a 3 minute residence time, followed by quenching with water prior to cooling inside the tubular nucleator. By appropriate selection of the temperature of the nucleation step, the number of nuclei formed in the tubular setup is accurately controlled. In this way, pure crystalline aspirin is continuously obtained with a desired mean crystal size between 3 μm and 300 μm and a reduced dispersion grade, avoiding seeding and micronisation steps.