Detection of the II–I Etiracetam solvent-mediated polymorphic transformation through the online monitoring of the suspension apparent viscosity

Although going to complex techniques can be useful at some stage of process development of crystallization processes, the goal of this article is to show that process control can also be achieved with relatively simple measurements, depending of course on what type of control is needed. Focusing on the Etiracetam crystallization process, this work demonstrates the potential of the online monitoring of the power dissipated in the suspension, a property that can be directly related to the suspension apparent viscosity for the detection of the solvent-mediated polymorphic transformation from form II to form I. Even if the work presented in this paper focused on a specific crystallization process, this easy-to-use method seems promising for the control of other crystallization processes exhibiting solvent-mediated polymorphic transformations with similar characteristics: (i) significant difference in the PSD of the crystals of the stable and the metastable forms, (ii) solid volumetric fraction in the suspension higher than 40% and (iii) absence of phenomena (breaking, attrition, agglomeration, secondary nucleation, etc.) interfering with the polymorphic transformation and affecting the PSD of the crystals.

► Our paper focuses on the Etiracetam crystallization process by cooling in a stirred tank.
► We show that process control can be achieved with relatively simple measurements. Such a measurement is the online monitoring of the suspension apparent viscosity.
► This technique allows to pinpoint the moment of the polymorphic transformation. Moreover, it allows identifying it as a solvent-mediated polymorphic transformation.