مدل سازی فرآیند، طراحی و ارزیابی تکنولوژیکی برای فرآوری پاراستامول مداوم

Continuous Pharmaceutical Manufacturing (CPM) has a strong potential to catalyse pharmaceutical innovation. This paper analyses Continuous Oscillatory Baffled Crystalliser (COBC) optimal design and performance for paracetamol crystallisation, via systematic modelling and nonlinear optimization (NLP). Clear trends emerge, with rate of antisolvent use having a marked impact of COBC volumes; crystal seed mass loading also has a strong effect. For the base case studied (inlet temperature of 50°C, seed crystal size of 40 microns) the optimal solution was for 2% seed mass loading (with respect to solute mass) and with 80% water antisolvent use (by mass with respect to process solvent acetone); the crystalliser size was 4.25 L with a total cost of 101,370 GBP, achieving a product yield of 50% with a product crystal size of 83.6 microns. Clear tradeoffs among mass efficiency, volume, cost and product crystal size have been illustrated, providing valuable quantitative insights into process performance.