(189e) Assessment of Blend Uniformity in a Continuous Tablet Manufacturing Process

Blend uniformity was monitored throughout a continuous manufacturing (CM) process by near infrared (NIR) spectroscopic measurements of flowing powder 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 as a cohesive active pharmaceutical ingredient (API) at a target level of 10.0% (w/w), silicified microcrystalline cellulose as the filler, and magnesium stearate as lubricant. The blender was operated at 250 rpm, where the system’s best performance was expected, 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. The results demonstrated that the drug concentration of powder blends obtained in the chute during this study were not representative of the drug concentration in tablets. However, 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. This study demonstrates that the feed frame is an ideal location for monitoring the drug concentration of powder blends for a continuous manufacturing system.