Comparative Investigation of Supersaturation and Automated Direct Nucleation Control of Crystal Size Distributions using ATR-UV/vis Spectroscopy and FBRM

The paper presents a thorough evaluation of different control strategies used in cooling crystallization, namely, unseeded linear cooling, seeded linear cooling, supersaturation control, and automated direct nucleation control. The sensitivity and robustness of supersaturation and automated direct nucleation control approaches are evaluated by varying different process parameters, such as seed loading and heating and cooling rates for the crystallization of paracetamol in isopropyl alcohol. The supersaturation control approach uses concentration information provided by ATR-UV/vis spectroscopy, while the direct nucleation control approach is based on focused beam reflectance measurements. Various statistics were used to assess the performance of each approach and it has been shown that the automated direct nucleation control approach, which requires no prior information about the system, outperformed the other control strategies. For the paracetamol in isopropyl alcohol system, significant variations were ...

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