Investigating the Design and Implementation of an In-Line Near-Infrared Probe Using Computational Fluid Dynamics for Measurement of Non-Newtonian Fluids

Abstract

Process analytical technology (PAT) has developed significantly since its introduction in pharma where many in situ analytical probes and measuring devices are now commercially available, replacing the use of off-line quality control measurements that are typically laborious and time intensive. The use of PAT instrumentation should not interfere with the process itself and subsequently should have no effect on the product whilst measuring representative samples. Implementation of these devices is typically arbitrary using empirical means. Therefore, the objective of this study is to highlight the use of computational fluid dynamics modeling to investigate the effect of interfacing parameters and process parameters of an inline near-infrared (NIR) probe used to determine the viscosity of a non-Newtonian micellar liquid. The parameters investigated for the probe were immersion depth, immersion angle, gap size, and fluid velocity. The results conclude that the immersion angle and depth should both be optimized to prevent stagnant fluid accumulating in the measuring gap ensuring that the NIR measurements are representative of the bulk. The gap size determines the optical pathlength and therefore was also investigated against an existing predictive viscosity model showing no changes in model performance with varying gap size. The use of computational modeling to develop a digital twin prior to PAT implementation at the equipment design stage ensures the technology can perform at its best and will also aid in calibration transfer studies.

Real-Time Monitoring of Crystallization Processes Using a Novel Compact Composite Sensor Array

“…PAT monitoring is governed by the same principles as those defined by the theory of sampling. ,, Although the literature shedding light on the impact of the position of PAT probes used to monitor liquids is limited, it is well-recognized that the lack of mixing and poor choice of probe angle and depth might lead to spatial heterogeneity of suspended particles in stirred crystallizers/tanks. ,,− Particularly, it has been demonstrated that the signal quality for probe designs with flow-through gaps/slids/cells, as employed in the CCSA (Figure S3 in the Supporting Information), , strongly depends on the hydrodynamic conditions influenced by the probe orientation, angle, and immersion depth. , Arbitrary placement of PAT probes can lead to stagnant liquid accumulating in the probe gaps/slids/cells resulting in nonrepresentative and fluctuating measurements of the bulk properties . In the present work, it was attempted to align the cell of the CCSA probe along the liquid motion in the crystallizer (Figure S3 in the Supporting Information) to permit unrestricted flow through the measuring cell without claiming to have achieved optimized conditions.…”

“…23,37,74−76 Particularly, it has been demonstrated that the signal quality for probe designs with flow-through gaps/slids/ cells, as employed in the CCSA (Figure S3 in the Supporting Information), 37,38 strongly depends on the hydrodynamic conditions influenced by the probe orientation, angle, and immersion depth. 24,73 Arbitrary placement of PAT probes can lead to stagnant liquid accumulating in the probe gaps/slids/ cells resulting in nonrepresentative and fluctuating measurements of the bulk properties. 73 In the present work, it was attempted to align the cell of the CCSA probe along the liquid motion in the crystallizer (Figure S3 in the Supporting Information) to permit unrestricted flow through the measuring cell without claiming to have achieved optimized conditions.…”

“…24,73 Arbitrary placement of PAT probes can lead to stagnant liquid accumulating in the probe gaps/slids/ cells resulting in nonrepresentative and fluctuating measurements of the bulk properties. 73 In the present work, it was attempted to align the cell of the CCSA probe along the liquid motion in the crystallizer (Figure S3 in the Supporting Information) to permit unrestricted flow through the measuring cell without claiming to have achieved optimized conditions. For the latter, computational fluid dynamics modeling is recommended, 73,77 which was beyond the scope of this study.…”

“…73 In the present work, it was attempted to align the cell of the CCSA probe along the liquid motion in the crystallizer (Figure S3 in the Supporting Information) to permit unrestricted flow through the measuring cell without claiming to have achieved optimized conditions. For the latter, computational fluid dynamics modeling is recommended, 73,77 which was beyond the scope of this study. Thus, the subjective placement of the CCSA for each crystallization experiment after cleaning and reassembling might have contributed to the data scattering observed in some experiments.…”

“…PAT monitoring is governed by the same principles as those defined by the theory of sampling. 2,69,72 Although the literature shedding light on the impact of the position of PAT probes used to monitor liquids is limited, 73 it is well-recognized that the lack of mixing and poor choice of probe angle and depth might lead to spatial heterogeneity of suspended particles in stirred crystallizers/ tanks. 23,37,74−76 Particularly, it has been demonstrated that the signal quality for probe designs with flow-through gaps/slids/ cells, as employed in the CCSA (Figure S3 in the Supporting Information), 37,38 strongly depends on the hydrodynamic conditions influenced by the probe orientation, angle, and immersion depth.…”