Development of a continuous evaporation system for an API solution stream prior to crystallization

A bubble column was investigated as a method to achieve a desired and controllable rate of evaporation of a pharmaceutical solution. Applying a thermodynamic model to predict the rate of evaporation, all predicted values were observed to have accuracies within the bounds of instrumentation errors (<5% absolute). The developed model accounted for the measured effect of reduced vapor pressure, caused by the dissolved solids as a function of their concentration. A general method to obtain accurate measurement of this effect is introduced and applied, improving the accuracy of model predictions. Consistent and repeatable evaporation rates ranging from 0.7 to 6.9 g/min were achieved experimentally, and errors between predicted rates and observed ranged from 0.219% to 4.19% absolute. This demonstrates a controllable and flexible method for the evaporation of process streams which can be compared to harsher conventional methods such as boiling. The column was configured in a continuous mode and coupled to a downstream crystallizer (MSMPR). Using the column as a controllable concentrator, the concentration of a dilute feed stream of paracetamol in methanol was increased in a single equilibrium stage. The column demonstrated the ability to concentrate the solution in flow by 179%, delivering a flow of 2 ml/min of concentrated liquor to the MSMPR. The MSMPR achieved steady-state of control, measured by offline dissolved concentration analysis and particle count by FBRM in situ, highlighting the applicablity of the column to perform reliably in a continuous tandem.