Evaluation of a compact composite sensor array for concentration monitoring of solutions and suspensions via multivariate analysis

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.…”

“…The CCSA signals at 280, 340, 600, and 860 nm generated by light-emitting diodes (LEDs) were recorded in situ and in real-time at 0.4 s intervals (preset using the Incentive Vision Monitoring software, v. 1.1) from the flow-through cell in the probe head (Figure S3 in the Supporting Information). , The raw CCSA signals were pretreated before further analysis using the OriginPro software (OriginLab Corporation, v. 9.7.5.184). To remove the signal interference from the Raman spectrometer recorded by the CCSA (Figure S4 in the Supporting Information), the Envelope function was employed with a smoothing window of 12 s (Figures S5–S7 in the Supporting Information) .…”

“…All crystallization experiments were performed in a five-neck 50 mL jacketed beaker (ACE Glass Inc.) equipped with an overhead stirrer at 300 rpm (J-Kem Scientific, OHS-1M) and a recirculating water bath (Julabo, F32-ME), as reported in the literature (Figure ). , The PAT probes of the CCSA (Incentive Vision IR/UV, ITA-Instruments Ltd.) and the RamanRxn2 multichannel analyzer (immersion probe, Kaiser Optical Systems, Inc.) were inserted into the jacketed beaker, near the impeller blade. , The entire jacketed beaker was shielded with aluminum foil to eliminate external light exposure. ,, …”

“…In the past two decades, numerous studies have been reported applying PATs in solution crystallization processes for in situ monitoring of, e.g., concentration, suspension density, crystal size, shape, and solid form. − ,,, However, these mostly spectroscopic-based techniques demand significant capital investments and are costly to maintain within “hostile” manufacturing environments, away from the well-protected research and development (R&D) laboratories, to be used as process analyzers. , Perhaps, for these reasons, sophisticated PATs with their typically bulky size resulting in larger space requirements are mostly documented for laboratory-scale applications. ,, Consequently, there is a general desire to reduce the costs of PATs, which has driven various research initiatives on innovative PATs and process analyzers in recent years, , including those focused on crystallization monitoring quantitatively ,,, or qualitatively. ,,,,, Moreover, small, compact composite PAT probes have been identified as a priority by the Enabling Technologies Consortium comprising 12 pharmaceutical companies . Such compact composite probes are considered to alleviate space constraints in milliliter-scale crystallizers ,,− while reducing their impact on the hydrodynamics …”

“…To address the needs for small-scale process analyzers capable of qualitatively monitor crystallization processes, ,,, a compact composite sensor array (CCSA) was evaluated in this study. Specifically, the CCSA combines four LED wavelengths, spanning the ultraviolet (UV) and near-infrared (NIR) region (280, 340, 600, 860 nm), and temperature measuring capabilities (thermocouple type R) in a 380 × 30 mm housing (length × diameter, 7 mm diameter at the probe head). , Our previous study demonstrated that the CCSA can accurately measure solution and suspension concentration in aqueous formulations. Both are important parameters in solution crystallization processes. ,,,,, …”