(509f) Dampening Effect of Feedrate Variation By Downstream Unit Operations in Pharmaceutical Continuous Manufacturing

Purpose: Direct compression is the most straightforward continuous approach to tablet manufacturing and is appealing for its simplicity. The process begins with feeding individual raw materials into a continuous blender and finally a tablet press. Loss-in-weight feeders are typically used to maintain constant flow rate for both APIs and excipients. The materials then are blended to achieve an axial uniform distribution of the API and excipients. The material exiting the blender is then sent directly to a tablet press where the blend is compacted into tablets. Therefore, any perturbations to mass flow exiting the feeder can be transferred down to the subsequent unit operations. The blender is designed to reduce some of the inherent fluctuation due to back-mixing, but it is not currently known how much variation in flow can be filtered. Another location where mixing can occur is located in the feedframe of the tablet press. In this work, the aim is to study the dampening effect of blender and feedframe on incoming feed rate variability from the feeders. Method: A formulation including API, excipients and lubricant will be used in this study. All the materials are fed using loss-in-weight feeders at the designed mass flows. Controlled changes to the mass flow rate of the API feeder will be performed at different levels of amplitude and time to force a fluctuation in flow. To determine the impact of each the blender and the feedframe, a NIR probe will be fixed in the continuous line, scanning material exiting the blender and before it enters the feedframe. Tablets will be collected and scanned by offline NIR to determine the effect of the feedframe on the dampening of the perturbations. Results and Conclusion: A funnel plot is obtained from the results from NIR analysis and tablet content, which shows that variation in API concentration in the blends are significant reduced compared to that in feeding. Feedframe also contributes to the dampening effect of variation in tablet uniformity at different magnitude of disturbance in incoming feedrates.