Monitoring powder potency and homogeneity is important in achieving real-time release testing in a continuous tablet manufacturing operation. If quality related issues are encountered, monitoring powder potency inside a feed frame offers a last opportunity to intervene in the process before tablet compression. Feed frame monitoring methods based on near infrared (NIR) spectroscopy have been increasingly reported in recent years. New process analytical tools with the potential of being deployed alone or in combination with NIR spectroscopy for feed frame monitoring are now available commercially. The present study evaluated the potential of near infrared chemical imaging (NIR CI) for in-line monitoring of a prototype pharmaceutical composition containing ascorbic acid (AA), microcrystalline cellulose and dicalcium phosphate. NIR spectroscopy was the reference method. In-line calibration models based on partial least square regression were developed and validated with a range of AA concentrations. The ability of NIR spectroscopy and NIR CI to predict concentrations in test runs was ascertained both independently and in combination. NIR CI, with a single bandpass filter, predicted AA concentrations—present at commercially relevant concentrations—with acceptable accuracy. Comparative results showed that NIR CI has the potential for in-line monitoring of blend concentrations inside feed frames. In addition to the advantage of increased sample size, it also has the potential to detect segregation inside feed frames.

Keywords: NIR spectroscopy, NIR CI, PAT, feed frame, in-line monitoring