Optical coherence tomography as a process analytical technology for oral film formulations

In oral film manufacturing, the dose of the active pharmaceutical ingredient is set by cutting the cast film into portions of defined area, which makes film thickness a critical quality attribute and an attractive target for calibration-free in-process measurement. This study evaluated Optical Coherence Tomography (OCT) to monitor film thickness of oral films along the offline-to-inline continuum. A galvanometer-scanning spectral-domain OCT system, acquiring full two-dimensional cross-sections, was applied offline to cast films and inline above the moving, dried film of a continuous coating line. An OSeeT Pharma 1D sensor, which acquires depth profiles at a fixed lateral position and evaluates the interfaces within the instrument, was operated on a custom-built conveying bench reproducing continuous film movement. Offline, OCT resolved internal defects, including air bubbles, insoluble inclusions and the interlayer boundary of bilayer films. Preliminary observations further indicated its potential to detect storage-related microstructural changes. OCT consistently yielded higher thickness values than a manually operated micrometer screw, with potential contributing factors, including film compression during contact measurement and the assumption of a constant refractive index, being discussed. Inline, thickness variations induced by deliberate variation of pump rate, coating knife height and liner speed were resolved for three different polymeric film formers, with thickness values extracted by post-processing of the recorded cross-sections, although evaluable frames were lost wherever the moving film left the set focal range. The OSeeT sensor returned stable thickness, roughness and homogeneity along the entire film length and reproduced the same systematic offset against the micrometer screw reference, delivering these values continuously and without post-processing. Structural information therefore remains available alongside continuous monitoring if the acquisition is configured to retain it. The main obstacles to the use of OCT as an inline Process Analytical Technology in continuous oral film manufacturing therefore lie in system integration, i.e. mechanical film guidance, automated onboard evaluation and image retention, rather than in the optical performance of the instruments.