(185e) Residence Time Distribution (RTD) Study of Chute Transition Zones between Unit Operations

Since continuous pharmaceutical manufacturing lines are unique to the manufacturing site, each manufacturing line can be wildly different even within the same company. One crucial tool utilized to ensure that the critical quality attributes of the final product in a continuous manufacturing (CM) line is the knowledge of the traceability or the residence time of material within the manufacturing line. Residence time distribution (RTD) is the measurement of time that a given amount of material resides in either a specific unit operation or throughout the entire continuous manufacturing line. Most of the RTD research concentrated on the RTD of the unit operations of CM and have either lumped in the connective parts, so they are included in a specific CM unit operation or have ignored the connection zones between each unit [1-6].

Since the main difference between the many different manufacturing lines available is transition zones, the work presented here has focused on traceability of material in transition zones to understand the effect of the distances between unit operations on the residence time distribution. In an integrated continuous manufacturing line, a blend of Compap L, Prosolv HD90, AcDiSol, and MgSt was dispensed into a transition chute where the hold up in the chute was controlled at three different levels. A pulse of Metformin was used as a tracer for the system. At the base of the set-up, in-line Near-Infrared detection was utilized to detect the tracer as it transitioned through the chute. The effect of critical process parameters was also investigated, such as throughput and blender speed, to capture a more detailed understanding of how the RTD is affected by the critical process parameters, specifically the transition zones.

Next, the effect of the tracer drop zone was investigated. The height at which the tracer falls into the system will affect the broadness of the RTD curve. Therefore, the height at which the tracer was introduced to the process stream was independently investigated. Since the material properties of the tracer can affect how the material falls, specifically as it displaces the air in the chute, three materials with a wide range of properties (i.e., cohesion, particle size, flowability) were selected as tracers to be introduced at different drop heights. Mass throughput was investigated to determine how the speed of the powder may exacerbate the dispersion. In all cases, a predicted NIR model was utilized to predict the concentration of the tracer as it transitioned passed the NIR probe. Using the concentration profile generated by the predictive model, the RTD parameters were regressed from the experimental data and compared using ANOVA to determine the effect of the critical process parameters. The results show that transition zones play a large part in RTD in a continuous line, greatly delaying pulse detection. In addition, the drop height of the pulse into one such transition zone can introduce noise into the residence time distribution, for which should be accounted.

References

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