Real-time monitoring of multiparticulate coating processes at industrial-scale is a critical demand for continuous and batch-wise process technologies. A combination with ultra-high-resolution optical coherence tomography is indeed a brilliant idea. Results were recently published by Wolfgang et al. [1]
Previous challenges in PAT of multiparticulate systems
This study presents a significant advancement in pharmaceutical process analytical technology (PAT) by introducing an industrially viable method for real-time, in-line monitoring of multiparticulate coating processes using ultra-high-resolution optical coherence tomography (UHR-OCT). Optical Coherence Tomography (OCT) is a non-invasive imaging technology that has already shown promise in monitoring pharmaceutical coating processes, particularly for tablets. However, its application in multiparticulate systems—like pellets and mini-tablets—has been limited due to technical challenges such as small particle sizes, thin coatings, and process-induced disturbances.
Multiparticulate dosage forms require coatings as thin as 2.5 microns, necessitating extremely high spatial and temporal resolution in the monitoring equipment. Traditional OCT systems struggled with this due to limitations in sensor stability, acquisition speed, and resolution. Previous attempts to apply OCT in such contexts were mostly proof-of-concept and not scalable to industrial levels. They also failed to monitor enough particles per minute to gather statistically relevant data for real-time quality assurance.
Real-time monitoring of multiparticulate coating processes
In this study, the authors successfully integrated a UHR-OCT system into two industrial fluid bed coaters: the Glatt MultiLab (Glatt GmbH, Binzen/Germany, 2 kg batch size) and Glatt GPCG PRO 30 (30 kg batch size). These coaters function based on the Wurster principle, which enables excellent particle separation and uniform coating application, making them ideal for high-quality coating processes. The novel sensor setup developed by the authors allowed for automated, high-resolution, real-time measurements of coating thicknesses ranging from 2.5 to 20 µm, even for diverse particles as small as 250 µm (CELLETS® 250-355, IPC, Dresden/Germany) up to 1000 µm (CELLETS® 700, IPC, Dresden/Germany) in diameter.
One of the key innovations was the design of a process interface that could withstand the dynamic and harsh environment inside fluid bed coaters, including challenges such as vibration and dust. This setup allowed for consistent data acquisition and evaluation across different batch sizes, proving its scalability and robustness. Reference measurements based on sprayed coating mass closely matched the OCT measurements, especially when particle agglomeration was minimal, further validating the accuracy of the system.
The study also involved image-based photometric analysis, which underscored the effectiveness of UHR-OCT in capturing fine details of the coating layers. The findings suggest that this method can serve as a powerful PAT tool for real-time release testing, quality assurance, and process optimization in industrial pharmaceutical manufacturing. By enabling precise monitoring of extremely thin coatings on small multiparticulates, this technology helps ensure product quality and efficacy while potentially reducing production costs and time.
Conclusion
In conclusion, the authors demonstrate that UHR-OCT is not only capable of meeting the demanding requirements of multiparticulate coating monitoring but also scalable and adaptable to industrial environments. This development marks a significant step toward broader adoption of OCT-based PAT tools in the pharmaceutical industry, particularly for advanced drug delivery systems involving small, coated particles.
References
[1] International Journal of Pharmaceutics (2025), 675, 125546. doi: 10.1016/j.ijpharm.2025.125546.
Glatt
