Economic Analysis of Continuous Crystallisation
Continuous manufacturing can offer significant operating and economic benefits to both laboratory- and production scale campaigns, compared to currently dominant, yet expensive and inefficient, batch methods. Continuous crystallisation designs offer reduced batch-to-batch variation, but may attain lower yields than their batch counterparts if not optimised. Technoeconomic analyses of different crystallisation configurations are valid methodologies for rapid screening of cost-optimal designs to elucidate attainable benefits over traditional batch methods. Process modelling and optimisation can be implemented for rapid, comparative evaluation of multiple configurations to establish the most promising continuous crystallisation designs. Mixed suspension-mixed product removal (MSMPR) and continuous oscillatory baffled crystallisers (COBCs) are feasible and viable continuous crystalliser designs with a variety of experimental and modelling studies presented in the literature demonstrating their viability as a simple alternative to batch crystallisers. This work describes the technoeconomic evaluation and optimisation of different crystallisation configurations for three active pharmaceutical ingredients (APIs): cyclosporine, paracetamol and aliskiren. Total cost minima are compared for different design scenarios (recycle consideration, number of implemented crystallisers, specified plant capacity) to elucidate cost-optimal designs. The current work highlights the effect of a variety of process considerations for crystalliser design and the importance of technoeconomic optimisation at the early stages of continuous crystallisation process development.