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

In this paper, we report a process control strategy for the production of metastable α-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 α-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.