Workflow for modelling and scale-down of industrial solvent swap distillations

Abstract

Solvent swap procedures are a common unit operation in API manufacturing. Their purpose is to exchange an original solvent with a chase solvent via distillation, typically to prepare the mixture for a subsequent reaction step or crystallization. When transferring these processes from laboratory to production scale, they frequently show discrepancies from planned values in terms of solvent consumption and batch duration. The physical regimes dominating at different scales differ (e.g., heat transfer limitations vs. evaporation kinetics). To address this, a structured, simulation-backed scale-down workflow is proposed to predict industrial plant behaviour and reduce operating costs.

The objective of this work is to develop and validate a structured scale-down workflow combining gPROMS process simulation with a 2L validation reactor. This workflow models cycle time, solvent consumption, and composition profiles for a 6300L industrial stirred-tank reactor before the production campaign. It is noted that product quality (e.g., thermal stability) must be evaluated through complementary experiments.