Modeling and Characterization of an in Situ Wet Mill Operation

The integration of an in situ wet mill and continuous mixed suspension mixed product removal crystallizer (MSMPR) is studied in this work for the cooling crystallization of paracetamol from an aqueous isopropanol mixture. The continuous operation was monitored using focused beam reflectance measurements (FBRM) to determine the onset of the steady state. The impact of various operational conditions of both continuous in situ mill and MSMPR unit is studied. The paper demonstrates that the operational conditions (i.e., residence time, operational temperature) of the crystallization process affect the achievable steady state product characteristics. In addition, the influence of in situ mill operating conditions (i.e., rotor speed) on important product and process qualities such as mean particle size, yield, and particle number is also discussed. Furthermore, breakage kernels were evaluated and validated through a parameter estimation routine. The in situ mill process can be assumed to be a combination of a nucleator generator and mill due to its impact on the mixing conditions as demonstrated by the parameter estimation framework. The model developed shows significant promise for process intensification and optimization studies in continuous crystallization process.