Real-time determination and visualization of two independent quantities during a manufacturing process of pharmaceutical tablets by near-infrared hyperspectral imaging combined with multivariate analysis.

Abstract

During pharmaceutical manufacturing, line-scan hyperspectral imaging enables us to collect several electromagnetic spectra at each pixel in a two-dimensional plane for each tablet. The present study quantitatively determines two independent values of the active pharmaceutical ingredient (API) content in a tablet and the amount of coating on a surface of the same tablet simultaneously; the process is visualized by means of a near-infrared hyperspectral imaging (NIR-HSI) system combined with multivariate data analysis at a typical manufacturing speed of 4,000 tablets per minute. The API content and the amount of coating were controlled to be in the range 80-120% and 0-7mg, respectively. The results of the cross validation of regression models demonstrated a coefficient of determination (R2) of 0.942, a root-mean-square error of cross validation (RMSECV) of 3.48% for the API content, an R2 of 0.939, and an RMSECV of 0.46mg for the amount of coating. These results demonstrated that the API content in a tablet as well as the amount of coating on the surface of the same tablet can be simultaneously determined with sufficient accuracy. This technique is practically applicable to process analytical technology in pharmaceutical manufacturing.