Pharmaceutical crystallization in Couette-Taylor crystallizer: A case study of polymorphism of amino acid L-glutamic acid

Abstract

The influence of intensity Taylor vortex flow in Couette-Taylor crystallizer on the crystallization of polymorphic amino acid L-glutamic acid was investigated in cooling crystallization. Here, the L-glutamic acid was chosen as the model crystal product, where it has two kinds of polymorphism including the unstable phase α-form and stable phase β-form crystal. In cooling crystallization, the α-form crystal transformed to the β-form crystal corresponding to the phase transformation of α-form to β-form crystal. The present study found that the selective polymorphism of α-form and β-form crystal as well as the phase transformation significantly depended on the intensity of turbulent Taylor vortex flow in Couette-Taylor crystallizer. Here, the selective β-form nucleation and phase transformation were remarkably promoted as increasing the rotation speed of inner cylinder in Couette-Taylor crystallizer. By comparison with the conventional stirred tank (ST) crystallizer, the Couette-Taylor (CT) crystallizer was at least 2.0 times more effective as regards the selective β-form polymorphism and phase transformation time. The advantage of CT crystallizer over the conventional ST crystallizer was explained in terms of the high shear stress and mass transfer of turbulent Taylor vortex flow in CT crystallizer. Here, the shear stress of Taylor vortex flow in CT crystallizer was at least 23.0 times higher than that of fluid motion in conventional ST crystallizer, whereas the mass transfer of Taylor vortex flow in CT crystallizer was at least 1.2 times higher than that of fluid motion in conventional ST crystallizer. As such, the high turbulent shear stress of Taylor vortex flow was expected to promote the β-form nucleation via the effective molecules alignment, whereas the high mass transfer of Taylor vortex flow facilitated the dissolution rate of α-form and growth rate of β-form crystal, resulting in an acceleration of phase transformation rate.

Development and characterisation of a cascade of moving baffle oscillatory crystallisers (CMBOC)

“…Therefore, it is not surprising that in the recent years increased research efforts have been made to develop and assess new crystallisers to achieve efficient process operation and enhanced particle control, these include mixed suspension mixed product removal (MSMPR) with single or multiple stages (cascade), plug flow reactors (PFRs) and Couette-Taylor crystallisers. [5][6][7][8][9][10][11][12] Also, well characterised experimental and digital design methodologies for process design, scale-up and optimisation of processes using these technologies have received considerable attention. 13 MSMPRs remain the most widely utilised platform for continuous crystallisation largely due to familiarity in terms of operation and control to existing batch equipment and these have been successfully operated at a range of scales from 1-10 L. 14 There are however, some recognised disadvantages of MSMPRs that include localised high shear near the impeller or agitator, non-uniform thermal control and nonlinear process scalability.…”