Near-infrared multivariate calibration updating using placebo: A content uniformity determination of pharmaceutical tablets

This paper presents an application of near-infrared (NIR) multivariate calibration for the determination of content uniformity of pharmaceutical tablets. Data used in this study were acquired from 3 NIR instruments obtained from 2 different vendors. One of these spectrometers is a dispersive NIR system configured for reflectance measurements while the other two, are Fourier transform (FT) based configured for both transmittance and reflectance. The performance of partial least squares (PLS) calibration models generated from the primary instrument (A) was investigated using samples measured on secondary instruments (B and C). The cross-instrument predictions without standardization or updating was not successful in the reflectance mode for both instrument B and C producing root mean square error of prediction (RMSEP) values of 2.78 and 5.78%, respectively. Similar deterioration of the calibration model was evidenced for instrument B in the transmittance mode with an RMSEP value of 2.65%. To minimize the effect of instrument response variations, piecewise direct standardization (PDS) was used. This lowered the RMSEP in the reflectance mode for the secondary instruments B and C to 1.19 and 1.58%, respectively. Similar improvement was obtained in the transmittance mode for instrument B producing RMSEP of 1.12%. For cases in which the stability of drug substance is poor and the on-demand manufacture of transfer samples is difficult, a model updating strategy that uses placebo samples is proposed. This technique also outperformed the direct cross-instrument predictions with RMSEP values of 1.25 and 1.70% for instruments B and C, respectively, in the reflectance mode and 1.42% for instrument B in the transmittance mode.