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.

连续制药制造（CPM）在催化制药创新方面具有强大的潜力。本文通过系统建模和非线性优化（NLP）分析了对乙酰氨基酚结晶的连续振荡折流结晶器（COBC）的最佳设计和性能。出现了明确的趋势，反溶剂的使用率对COBC量有显着影响；晶种的质量加载也有很强的作用。对于所研究的基本案例（入口温度为50°C，晶种尺寸为40微米），最佳解决方案是2％种子质量负载（相对于溶质质量）和80％的水抗溶剂用量（相对于工艺溶剂丙酮）；结晶器尺寸为4.25 L，总成本为101,370英镑，产品收率为50％，产品晶体尺寸为83.6微米。