Figures of Merit Comparison of Reflectance and Transmittance Near-Infrared Methods for the Prediction of Constituent Concentrations in Pharmaceutical Compacts

Abstract

The purpose of this work was to demonstrate how multivariate figures of merit, in conjunction with accuracy and precision statistics, can be used to evaluate the performance of near-infrared reflectance and transmittance spectroscopy for the nondestructive chemical quantification of intact pharmaceutical compacts. A total of 174 four-component compacts were produced at five compaction pressures following a fully balanced quaternary design. Near-infrared spectra were measured in both reflectance and transmittance modes. Partial least-squares regression was used to model spectroscopic response, and net analyte signal theory was used to generate the figures of merit. It was discovered that sample positioning variation more negatively impacted the performance (analytical sensitivity, S/N ratio, limit of detection) of the transmittance method. Process analytical technology implementation teams should consider these aspects during technology selection, method development, and validation.