At-line validation of optical coherence tomography as in-line/at-line coating thickness measurement method

Abstract

Optical Coherence Tomography (OCT) is a promising technology for monitoring of pharmaceutical coating processes. However, the pharmaceutical development and manufacturing require a periodic validation of the sensor's accuracy. For this purpose, we propose polyethylene terephthalate (PET) films as a model system, which can be periodically measured during manufacturing coating monitoring via OCT. This study proposes a new approach addressing the method validation requirement in the pharmaceutical industry and presents results for complementary methods. The methods investigated include direct measurement of the layer thickness using a micrometer gauge as reference, X-ray micro computed tomography, transmission and reflectance terahertz pulsed imaging, as well as 1D-and 3D-OCT. To quantify the significance of OCT for pharmaceutical coatings, we compared the OCT results for commercial Thrombo-ASS and Pantoloc tablets with direct measurements of coating thickness via light microscopy of microtome cuts. The results of both methods correlate very well, indicating high intraand inter-tablet variations in the coating thickness for the commercial tablets. The light microscopy average measured coating thickness of Thrombo-ASS (Pantoloc) was 71.0 µm (83.7 µm), with an intercoating variability of 8.7 µm (6.5 µm) and an intra-coating variability of 2.3 µm to 9.4 µm (2.1 µm to 6.7 µm).

Real‐Time Metrology for Roll‐To‐Roll and Advanced Inline Manufacturing: A Review

“…Optical Coherence Tomography (2.10) Thickness, Internal topography, refractive index [34] Polymers, semitransparent films, biological samples 1 m min −1 (not including data processing) [34] 1D OCT: frame rate of 97.66 fps; 3D OCT prototype: frame rate of 30.6 fps. [35] Vertical resolution: 5.8 microns; Lateral resolution: 91 microns @ web speed of 1 m min Has significant potential for R2R applications as it can be used in reflection and transmission mode [36] and complete probe/sensor can be integrated into a compact fiber package.…”

“…Wolfgang et al (2019) compared 1D and 3D OCT thickness measurement of pharmaceutical PET coatings to direct physical measurement using micrometer gauge as well as several other indirect noncontact techniques including light microscopy, X-ray micro-computed tomography, transmission, and reflectance terahertz pulsed imaging. [35] The commercial 1D OCT system manufactured by Phyllon was capable of 97.66 frames per second. The in-house developed 3D OCT system was capable of 30.6 frames per second.…”

Continuous In-Line Chromium Coating Thickness Measurement Methodologies: An Investigation of Current and Potential Technology

“…There are many different methodologies for monitoring coating thickness and each method is usually specific for an application dependent on the substrate and coating materials. There are several reported methodologies for thin film characterization for application in the photonics industry [ 9 ], metal finishing industry [ 10 , 11 ], medical industry [ 12 , 13 , 14 ], and semi-conductor industry [ 15 , 16 ]. The successful monitoring of coating thickness can produce results such as creating a product to the intended specification for the customer, cost savings resultant from the prevention of material wastage, and a greater yield output from the implementation of in-line control.…”

Development of modern drug identification technologies using laser technology, against drug counterfeiting

“…Presumably, due to their different geometry, they were mixed inappropriately during coating, therefore they might have different coating thicknesses. Tablet coating thickness may also vary in the case of identical tablets, as observed by M. Wolfgang et al, where it varied between 56.3 µm and 86.9 µm (Wolfgang et al, 2019). The literature also confirms that the shape of the tablet directly influences intra-tablet coating uniformity.…”