Seeding and Constant-Supersaturation Control by ATR-FTIR in Anti-Solvent Crystallization

Abstract

The strategy for seeding and supersaturation control can play a critical role in defining the purity and particle size distribution of crystal products. Previous research has demonstrated that operation of crystallizers at constant supersaturation by feedback control is attractive due to its simplicity and resistance to operating disturbances. In this study, the effects of seed loading and seed size distribution were investigated for anti-solvent crystallization of paracetamol from a water-acetone mixture operated at constant supersaturation. A seeding strategy based on a simple mass balance equation provided a good starting point for the refinement of particle size distribution and adjustment of batch time in different circumstances to obtain a target average crystal size with narrow size distribution.

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.…”

Supersaturation tracking for the development, optimization and control of crystallization processes

“…This is a crystallization process to which no seed is added, but where the system is allowed to spontaneous nucleate in a supersaturated environment. From the literature, the key benefits of self-seeding include an increase in product dimension and a reduction in the agglomeration of the solute (Yu et al, 2006). As shown above, the final particle dimension for benzoic acid is heavily influenced by the primary metastable zone width, with the smaller zone width (here obtained for the slow cooling rate) giving the larger crystal size.…”

“…Much focus has recently been given to the extension of quantitative ATR-FTIR models to supersaturation setpoint control (Cote et al, 2009;Nagy et al, 2008;Yu et al, 2006;Fujiwara et al, 2005). Extending the presented supersaturation methodology to supersaturation setpoint control is assessed here.…”

Improving of Crystal Size Distribution Control Based on Neural Network-Based Hybrid Model for Purified Terephthalic Acid Batch Crystallizer

“…Production of a uniform and reproducible CSD is a main difficulty in batch crystallization [20,21]. There are several approaches proposed in the literature; nevertheless, one way to improve the control of CSD is to use supersaturation control (SSC) [22][23][24], which drives the process within the metastable zone to avoid nucleation. Therefore, model-based approaches, i.e.…”