Measurement of the Intertablet Coating Uniformity of a Pharmaceutical Pan Coating Process With Combined Terahertz and Optical Coherence Tomography In-Line Sensing

Abstract

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.

Review of Terahertz Pulsed Imaging for Pharmaceutical Film Coating Analysis

“…In particular, OCT is well suited for thin coatings 10-60 µm, while TPI is suitable for 40 µm and above. This is reinforced in [41], which also showed how coating refractive index at optical frequencies could be extrapolated from the absolute thickness measured using TPI [42]. Ultimately, the upper limit for OCT measurement is bound by the optical properties of the coating formulation [43].…”

“…As process investigation on the production-scale are wasteful and expensive, a lab-scale coating unit was purposely built, retrofittable to the TPI [41], shown in Figure 5. Uniquely, the coating unit also included provisions for in-line OCT sensing, which as a whole allows coating thicknesses from as low as 20 µm and up to 300 µm and above to be measured and also with different coating formulations.…”

“…Time average of the coating thickness measured by the respective sensors independently where thin coatings can be resolved by OCT and thicker coatings with TPI. Reprinted from [41] with permission from Elsevier.…”

Investigating liquid water distribution in Nafion polymer electrolyte membrane with terahertz imaging

“…THz radiation can penetrate through optically opaque dielectric materials, such as polymers [5], while being strongly attenuated by liquid water [6] thus making THz imaging techniques attractive for non-destructive quality control applications [7][8][9]. With the recent availability of a compact, low-cost THz camera, as a first step toward PEMFC inspection, this paper explores the feasibility of a compact THz imaging system for inspecting liquid water in Nafion® PEMs.…”

Characterization of the coating and tablet core roughness by means of 3D optical coherence tomography

“…The very high acquisition rate of OCT (up to MHz depth scan rates (Wieser et al, 2010)) renders this method a promising tool for the in-line monitoring of coating processes. This has been reported for the coating of tablets in a pan coater (Markl et al, 2015a;Lin et al, 2017) as well as the coating of pellets in a fluid-bed coater (Markl et al, 2015c). Different data processing procedures have been developed to rapidly analyze the OCT measurements and to determine the coating thickness at several positions of individual tablets (Markl et al, 2015b, Lin et al, 2015.…”