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

Abstract

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 thermodynamic 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. Predicting the rate of evaporation using the developed model, consistent and repeatable evaporation rates ranging from 0.7 -6.9 g/min were achieved, and errors between predicted rates and experimental ranged from 0.219% to 4.19% absolute. This demonstrates a more controllable and flexible alternative to the evaporation of process streams compared to 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 an output of 2 mL/min to the MSMPR. The MSMPR achieved steady-state of control, measured by offline This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as

Binary Solvent Swap Processing in a Bubble Column in Batch and Continuous Modes

“…This highlights that the assumption of minimal resistance to mass transfer on the gas side is valid under the tested conditions. 9 , 10 The model can therefore be applied as a generic approach for predicting the rate of evaporation with known vapor–liquid equilibrium data and fixed process parameters.…”

“…From previous work, 10 it was known that the introduction of a dissolved solute would cause a reduction in the vapor pressure of the solvents, and this effect would need to be measured. Comparing the pure vapor pressure profile to that of the reduced vapor pressure, a reduction in vapor pressure was measured as appreciably constant across the entire range of temperatures tested for both acetone and IPA at a dissolved solute concentration of 10%.…”

“…13,14 The vigorous mixing also achieves good rates of heat and mass transfer between the two phases 15,16 and often allows the exiting gas stream to reach equilibrium with minimal contact time required between the two phases. 9,10,17 bubble columns at temperatures appreciably lower than their respective boiling points.…”

“…The application of a bubble column may be a suitable option to achieve a controlled continuous solvent swap. , Aeration and bubbling methods are used extensively in the chemical and biopharmaceutical industry because of the high interfacial areas and good mass transfer that they provide between phases. They are frequently employed in wastewater treatment facilities for the biological oxidation of organic waste and as a method to remove trace volatile organic compounds and ammonia .…”

“…High levels of mixing are achieved by the vigorous introduction of the gas phase into the system. This often results in thermally homogeneous operation between the two phases, minimizing the likelihood of hot-spot formation at heat-exchanging surfaces. , The vigorous mixing also achieves good rates of heat and mass transfer between the two phases , and often allows the exiting gas stream to reach equilibrium with minimal contact time required between the two phases. ,, This saturated vapor is what provides the good rates of evaporation achieved by bubble columns at temperatures appreciably lower than their respective boiling points.…”