Real-time monitoring of multiparticulate coating processes at industrial-scale using ultra-high-resolution optical...

Optical Coherence Tomography (OCT) has been reported as a promising technology for in-line monitoring of pharmaceutical film-coating processes, providing real-time information on actual tablet coating thicknesses and thickness variability, together enabling correlation modeling of the dissolution behavior. However, an increasing interest in the in-line investigation of multiparticulates demands further evolution of the technology and new concepts for process interfacing. To achieve this, we present a novel way to interface OCT to the relevant coating processes using a cutting-edge industry-ready ultra-high-resolution OCT (UHR-OCT) for in-line monitoring. Based on the setup, real-time in-line data of multiparticulate coating processes was acquired, enabling an automated coating thickness evaluation starting at the low micron range. The system was tested with two different core sizes of 250- and 700-µm mean diameter, coated in two different coaters, namely a Glatt MultiLab (2 kg batch size) and a Glatt GPCG PRO 30 (30 kg batch size). Coating thicknesses were successfully measured directly in the process in real-time within a range from 2.5 to 20 µm. Reference measurements based on sprayed coating mass showed excellent agreement between OCT and the reference when agglomeration was negligible. Additionally, conducted image-based photometry emphasizes the capabilities of UHR-OCT as a powerful technology for multiparticulate coating monitoring. The presented approach was found to be stable, batch size-independent, and translatable to an industrial setup. Moreover, it extends the capabilities of OCT toward a versatile process analytical technology to monitor even the thinnest coatings and small particles used in pharmaceutical coating processes.