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

Matthias Wolfgang, Anna Peter, Patrick Wahl, Daniel Markl, J. Axel Zeitler, Johannes G. Khinast

Research output: Contribution to journalArticle

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, to periodically validate the measurements during manufacturing. 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 intra- and 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 inter-coating 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).

Original languageEnglish
Article number118766
JournalInternational Journal of Pharmaceutics
Volume572
Early online date6 Nov 2019
DOIs
Publication statusPublished - 15 Dec 2019

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Keywords

  • coating thickness variability
  • optical coherence tomography (OCT)
  • reference material
  • terahertz pulsed imaging (TPI)
  • X-ray micro computed tomography (XµCT)
  • OCT

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