In the pharmaceutical industry, batch crystallization processes at production scale are not always well understood. Several factors have a significant impact on the process of crystallization, such as the physicochemical properties (solubility curve and super-saturation level), the crystal seeding (amount, purity and specific area), the engineering design (crystallizer and propeller), and the control (heating, cooling and stirring rates) [1]. When these factors are poorly understood or insufficiently controlled, they may produce batch-to-batch inconsistencies in terms of size distribution or polymorphic structure of crystals, and lead to pharmaceutical products that may be out of specifications. Online spectroscopic techniques are widely used in industry as they allow to acquire data in real-time, without any sampling, quenching or dilution procedure. Near-infrared (NIR) and attenuated total reflectance (ATR) ultraviolet visible (UV-vis) spectroscopy are two of these online spectroscopic techniques that are routinely used in industry to test, validate and monitor batch crystallization processes [2,3].

[1] Billot et al, "A Review of the use of process analytical technology for the understanding and optimization of production batch crystallization processes" Org. Process Res. Dev., 2010, 14, 511-523
[2] Fevotte et al, "Applications of NIR spectroscopy to monitoring and analyzing the solid state during industrial crystallization processes" Int. J. Pharm., 2004, 273, 159-169
[3] Barrett et al, "Application of ATR-UV spectroscopy for monitoring the crystallization of UV absorbing and non-absorbing molecules" Org. Process Res. Dev., 2005, 9, 348-355