Light Leakage Effects with Different Sample Holder Geometries in Quantitative Near-Infrared Transmission Spectroscopy of Pharmaceutical Tablets

Abstract

Transmission geometry is becoming an alternative to the conventional reflectance geometry in near-infrared (NIR) spectroscopy of pharmaceuticals. An advantage of transmission NIR is that it samples a volume whereas reflectance NIR merely samples the surface region of solid preparations. This leads to more representative measurements on complex matrices, such as some types of tablets. However, more attention must be paid to sample presentation with respect to light leakage. An investigation of the effects of the light leakage obtained with different sample holder geometries on content calibrations for transmission NIR on tablets was performed. Two different model samples, a composite and a compact tablet, were measured in sample wells in which the diameters and heights were varied according to a multivariate design. This was done in order to simulate a mismatch between the tablet and the sample well. Partial least-squares (PLS) models were built and used to evaluate the significance of the sample well geometry. Liquid chromatography was used as a reference method. As expected, for both types of tablets it was found that a small mismatch in tablet-to-well diameter deteriorated the repeatability of the NIR spectra, although, unexpectedly, this gave the best predictions and more robust models. In all, this indicates that light leakage should not be minimized at calibration, but included as a factor in the multivariate model that spans the future expected variation in light leakage.