Comparison of Terahertz Pulse Imaging and Near-Infrared Spectroscopy for Rapid, Non-Destructive Analysis of Tablet Coating Thickness and Uniformity

Abstract

In this study, coating thickness and uniformity of production-scale pharmaceutical tablets were investigated using near-infrared (NIR) and terahertz pulse imaging (TPI) spectroscopy. Two coating formulations were considered; samples for each coating formulation were obtained at 0, 1, 2, 3, 4, and 5% coating weight. NIR spectra were collected, and regressed with respect to batch percent weight gain. While standard errors of calibration (SEC) less than 0.5% were observed for both formulations, the calibrations were not specifically sensitive to coating thickness. An upper limit for NIR coating thickness analysis was estimated to be~4 -6% weight gain for this system. The NIR calibrations were used as filters to choose subsets of samples for TPI, and as a secondary method for validation of TPI results. The features in TPS time-domain spectra result when an incident THz plane wave meets a refractive index interface, which may be converted to an absolute distance. Therefore, assuming that a discernible difference in refractive index between coating material and core exists, coating thickness can be determined non-destructively. Coating thickness measurements from TPI and NIR spectroscopy were compared to estimate the lower limit for quantitative TPI coating analysis; a lower limit of~35 mm was obtained for this system. Optical microscopy was employed on a subset of samples to validate absolute thickness values; reasonable correlations between the three methods were obtained. TPI was considered advantageous relative to the other methods, as similar results were obtained without the need for destructive sampling or empirical calibration development.

Development of a Process Analytical Technology (PAT) for in-line monitoring of film thickness and mass of coating materials during a pan coating operation

“…Terahertz Pulsed Imaging (TPI) was described as a powerful alternative for coating thickness determination due to its non-destructive nature and its ability to provide a three dimension map of coating thickness over the whole tablet surface (Fitzgerald et al, 2005;Ho et al, 2007;Zeitler et al, 2007). Some authors concluded that this method could only be applied to the monitoring of thickness values higher than 35 lm due to the detection limit of the instrument (Cogdill et al, 2007;Maurer and Leuenberger, 2009). For the present study, since specifications for dissolution rate requires high polymer deposits (Siepmann et al, 2007), TPI could be selected as a relevant reference method.…”

Review of Terahertz Pulsed Imaging for Pharmaceutical Film Coating Analysis

“…The lateral resolution is limited by the wavelength of terahertz radiation, for example 150 and 400 µm at 1 and 2.7 THz, respectively [10,13], and the depth resolution is limited by the terahertz pulse duration of <200 fs. The achievable lateral resolution for pharmaceutical tablets is typically between 150-250 µm, at approximately 1.5 to 2.7 THz frequency range, and 30-40 µm for the depth resolution [6,7,10,14,15]. Investigations on improving spatial resolution of a THz-TDS system have been presented elsewhere [16][17][18].…”

“…The ability of TPI to measure the absolute coating thickness has made it an attractive reference method for comparison and calibration against various PAT. For example, it has been compared against the well-established NIR spectroscopy for coating thickness and uniformity of production-scale pharmaceutical dosage forms [14]. Comparing the two techniques, NIR spectroscopy is an indirect measurement, where coating thickness needs to be correlated with the absorbance that in turn requires multivariate calibration using partial least squares (PLS) for quantitative analysis.…”

Delayed Release Tablet Dissolution Related to Coating Thickness by Terahertz Pulsed Image Mapping

“…The system has been described in detail by Zeitler et al 20 The precision and reproducibility have been studied in detail. [22][23][24] The reflected time-offlight radiation is analyzed in the time domain to measure the thickness of the tablet coating at points nominally 250 mm apart over the surface. Reflections occurs whenever there is a change in refractive index.…”