(381c) Polymorphism Control Via Combined Cooling and Antisolvent Crystallization in Continuous Mixed Suspension Mixed Product Removal Crystallizers

This work
proposes a model based polymorphism control in 2-Aminobenzoic acid system via
combined cooling and antisolvent crystallization (CCAC) in continuous mixed
suspension mixed product removal (MSMPR) crystallizers. A systematic approach
is devised to achieve a specific polymorph in the three dimensional space of
the operating variables – temperature, solvent composition and residence time.
The solubility of the two polymorphs is determined at different temperatures^a
and solvent compositions by thermogravimetric method. The induction and
polymorph transformation times are studied to identify the operational window
of residence times. The polymorphic crystallization process is modelled using
population balance equations (PBEs) in which nucleation, growth and dissolution
kinetics are considered to account for solvent mediated polymorphic
transformation. A systematic experimental design is applied to estimate the
kinetic parameters. The growth rate of the stable polymorph (form I) at a
particular supersaturation was found to increase with increase in solvent
content (isopropyl alcohol) in the solution. The estimated kinetic parameters
are applied to the population balance model for the polymorphic system for the
calculation of optimal temperature, solvent composition and residence time in
continuous CCAC for achieving a specific polymorphic form. The presentation
will show the detailed systematic approach to control polymorphism via CCAC in
continuous MSMPR crystallizers and experimental validation of the model.

^aSimone, E., Saleemi,
A.N., Nagy, Z.K., 2014. Active polymorphic feedback control of crystallization
processes using a combined Raman and ATR-UV/Vis spectroscopy approach. Cryst.
Growth Des. 14 (4), 1839–1850