Combining ATR-FTIR and FBRM for feedback on crystal size

Crystallization operations are frequently used in a number of industries, in particular in the production of fine chemicals. However, stochastic and nonlinear crystallization kinetics often makes it difficult to determine appropriate operating procedures for producing the desired products. This has motivated the development of online measurement tools and the pursuit of feedback control strategies that can adapt to the observed kinetics and produce consistent products. One important crystal property that often must be controlled is the crystal size distribution. Although a number of feedback control schemes have been proposed to indirectly control the size of crystals, these strategies suffer from the lack of direct feedback on the crystal size during operations. Here we propose the simultaneous use of focused-beam reflectance measurements (FBRM) and attenuated total-reflectance Fourier-transform infrared absorbance (ATR-FTIR) measurements to obtain an online measure of average crystal size: the mass-per-count. In this paper, we give experimental results that indicate a strong correlation between the proposed mass-per-count measure and the average crystal size. Furthermore, we demonstrate the utility of this online measure for determining the effects of certain operations on the evolution of average crystal size. Finally, we use this measure to understand the effects of prevailing feedback strategies-known as supersaturation control and direct nucleation control-and, in doing so, elucidate a feedback control strategy that combines these techniques to produce large crystals more efficiently.