Assessment of blend uniformity in a continuous tablet manufacturing process

Abstract

Blend uniformity was monitored throughout a continuous manufacturing (CM) process by near infrared (NIR) spectroscopic measurements of flowing blends and compared to the drug concentration in the tablets. The NIR spectra were obtained through the chute after the blender and within the feed frame, while transmission spectra were obtained for the tablets. The CM process was performed with semi-fine acetaminophen blends at 10.0% (w/w). The blender was operated at 250 RPM, for best performance, and 106 and 495 rpm where a lower mixing efficiency was expected. The variation in blender RPM increased the variation in drug concentration at the chute but not at the feed frame. Statistical results show that the drug concentration of tablets can be predicted, with great accuracy, from blends within the feed frame. This study demonstrated a mixing effect within the feed frame, which contribute to a 60% decrease in the relative standard deviation of the drug concentration, when compared to the chute. Variographic analysis showed that the minimum sampling and analytical error was five times less in the feed frame than the chute. This study demonstrates that the feed frame is an ideal location for monitoring the drug concentration of powder blends for CM processes.

Keywords: Content uniformity; Continuous tablet manufacturing; Feed frame; Powder blend uniformity; Process Analytical Technology; Transitional chute.