Process Control of Seeded Batch Cooling Crystallization of the Metastable α-Form Glycine Using an In-Situ ATR-FTIR Spectrometer and an In-Situ FBRM Particle Counter

Abstract

In this paper, we report a process control strategy for the production of metastable R-form glycine crystals of a desired mean mass size by manipulating the alternating temperature profile and the final termination temperature. The seed crystals of the R-form glycine introduced were grown successfully to the size of the product with no fine crystals. Generation of the γ-glycine crystals (stable polymorph) was completely avoided. This crystallization method is flexible and easy to operate, because the alternating temperature profile can be determined on-site according to the transient supersaturation and particle count number data obtained from an in-situ ATR-FTIR spectrometer and an in-situ FBRM particle counter, respectively. The termination time or batch time was also determined on-site to a point that the residual supersaturation became zero. This on-site strategy-determination technique is expected to be applied widely for a variety of polymorphic systems other than the glycine-water system as a practical method for the selective crystallization of metastable polymorphs.

Optimal seed recipe design for crystal size distribution control for batch cooling crystallisation processes

“…One way to enhance the control of CSD is to use supersaturation control (SSC) (Aamir et al, 2009a;Braatz, 2002;Doki et al, 2004;Fujiwara et al, 2005;Liotta and Sabesan, 2004;Yu et al, 2006) or direct nucleation control (Abu Bakar et al, 2009aBakar et al, , 2009bWoo et al, 2009), which drives the process within the metastable zone to avoid nucleation, or to generate controlled nucleation/dissolution events, respectively. Although these approaches can provide improved consistency of the CSD, they do not address the actual design of the CSD.…”

Modelling and control of combined cooling and antisolvent crystallization processes

“…However, in more modern crystallization designs this concept has been extended, and it has been shown that driving the system into the undersaturated region can yield better crystal quality via controlled fine dissolution (Doki et al, 2004). Controlled in situ dissolution is also an efficient way for adaptive crystallization control, which can correct the effects of changes in operating conditions due to scale-up or disturbances (e.g., variations in seeding).…”

Inline‐Partikelgrößenmesstechniken für Suspensionen und Emulsionen

“…Aufgrund der Sensitivität des FBRM-Verfahrens gegenüber Form, Größe und Konzentration der Teilchen kann der zeitliche Verlauf der TGV inline in Kristallisations- [43,49] und on-line in Flockungsprozessen [50,51] untersucht werden. Weitere Anwendungsgebiete sind die Inline-Überwachung der Teilchengrö-ße in Suspensionspolymerisationen [47] und der Einsatz in der Meeresbiologie [41] sowie zur Inline-Prozesskontrolle in der pharmazeutischen Industrie [52].…”