(198d) Development and Application of Residence Time Distribution (RTD) Models for a Continuous Direct Compression Process

Continuous manufacturing platforms have recently raised popularity in the pharmaceutical industry because offer gains of economies of scale, lower operational complexity, higher product quality and process reliability. The development of a robust continuous process requires an in-depth understanding of the interactions between raw material/blend attributes and process parameters, and their impact on the product’s critical quality attributes so that a design space can be achieved.

In addition, advanced control systems and process analytical technologies must be in place to ensure consistent product quality and enable the product’s real-time release. To this end, a thorough study of the process dynamics is also needed to estimate the residence times required in each operation to obtain acceptable results and predict how material flow disturbances propagate through the manufacturing line and influence the final product. This characterization of process dynamics is usually performed with a residence time distribution (RTD) analysis of the line.

This work highlights the application of RTD models in the development of a Continuous Direct Compaction (CDC) process. It is shown how the RTD model of individual unit operations can be calibrated with a minimal set of experiments. Case studies are presented where the impact of variabilities in mass flows of feeders and blenders on assay profiles with different intensities and duration are analyzed. Results are discussed in the view of using RTD models to compare robustness of different process setups during process development and to design strategies for in-process control.