Measurement of Active Content in Escitalopram Tablets by a Near-Infrared Transmission Spectroscopy Model that Encompasses Batch Variability

Near-infrared transmission (NIT) spectroscopy, with high-performance liquid chromatography as reference method, was used to study the variation of the active pharmaceutical ingredient (API), escitalopram, in five tablet batches (4%-12%, w/w) manufactured by direct compression. This study investigates the influence of sample orientation, powder segregation, and compression force on the NIT spectra. For this purpose, tablet samples were taken at six different production time points, at three different compression forces, and presented to the spectrometer in four different orientations and in three spectroscopic replicates. A total set of 2160 NIT spectra was recorded. The variances between the spectra at each level of API content were thoroughly investigated by partial least squares regression using theory of sampling. The results show that a minimum of 18 tablets from each level of API content is required to establish a robust NIT calibration. The identified number of spectra is required for covering small differences in the spatial heterogeneity of the API as well as minor variations in optical properties, due to variations in the tablet compression force. NIT spectroscopy is demonstrated to be a powerful technique not only for measuring the API content in escitalopram tablets but also for routine content uniformity analysis.