Abstract
A laminar-flow tubular crystallizer was used for seedless continuous flow crystallization of an active pharmaceutical ingredient, namely, Brivaracetam, which has a polymorphic behavior: rod-shaped crystals and a pseudo-polymorphic solvated, needle-like crystal. The combination of fast cooling at 20 °C/s and high supersaturation values between 4 and 11 resulted in the discrimination of nucleation and growth of only the desired crystalline form even though its solubility curve is very close to the one of the undesired needle shape. Crystal nucleation and the start of crystal growth occur inside the tubular crystallizer; high flow rates prevent clogging of the crystallizer. Further crystal growth may be, if desired, stopped via immediate filtration. In this way, an industrially applicable continuous crystallizer is proposed. It is also demonstrated that the presence of restrictions in the tubing drastically increases the nucleation rate. A literature survey points out that induced turbulence can occur under ...
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