Measurement of the intertablet coating uniformity of a pharmaceutical pan coating process with combined terahertz and optical coherence tomography in-line sensing

Hungyen Lin, Yue Dong, Daniel Markl, Bryan M. Williams, Yalin Zheng, Yaochun Shen, J. Axel Zeitler

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We present in-line coating thickness measurements acquired simultaneously using 2 independent sensing modalities: terahertz pulsed imaging (TPI) and optical coherence tomography (OCT). Both techniques are sufficiently fast to resolve the coating thickness of individual pharmaceutical tablets in situ during the film coating operation, and both techniques are direct structural imaging techniques that do not require multivariate calibration. The TPI sensor is suitable to measure coatings greater than 50 μm and can penetrate through thick coatings even in the presence of pigments over a wide range of excipients. Due to the long wavelength, terahertz radiation is not affected by scattering from dust within the coater. In contrast, OCT can resolve coating layers as thin as 20 μm and is capable of measuring the intratablet coating uniformity and the intertablet coating thickness distribution within the coating pan. However, the OCT technique is less robust when it comes to the compatibility with excipients, dust, and potentially the maximum coating thickness that can be resolved. Using a custom-built laboratory scale coating unit, the coating thickness measurements were acquired independently by the TPI and OCT sensors throughout a film coating operation. Results of the in-line TPI and OCT measurements were compared against one another and validated with off-line TPI and weight gain measurements. Compared with other process analytical technology sensors, such as near-infrared and Raman spectroscopy, the TPI and OCT sensors can resolve the intertablet thickness distribution based on sampling a significant fraction of the tablet populations in the process. By combining 2 complementary sensing modalities, it was possible to seamlessly monitor the coating process over the range of film thickness from 20 μm to greater than 250 μm.

Original languageEnglish
Pages (from-to)1075-1084
Number of pages10
JournalJournal of Pharmaceutical Sciences
Issue number4
Early online date23 Dec 2016
Publication statusPublished - 1 Apr 2017


  • coating thickness
  • coating uniformity
  • optical coherence tomography
  • pharmaceutical film coating
  • terahertz pulsed imaging
  • terahertz sensing

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