Effect of tracer material properties on the residence time distribution (RTD) of continuous powder blending operations. Part I of II: Experimental evaluation

Residence time distribution (RTD) models are essential to understand process dynamics and support process monitoring and control in continuous manufacturing systems. RTD models can also be used to monitor material traceability and to isolate intermediate materials or finished products when specifications are not met. However, while pharmaceutical companies are currently making extensive use of RTD approaches, standard methods for conducting, interpreting, and using RTD results in continuous pharmaceutical manufacturing have not yet been established by regulatory authorities. This paper seeks to facilitate generating such standards. We discuss in detail the assumptions and conditions that are relevant to the proper selection of tracers for RTD experiments, and demonstrate that tracer selection can have substantial impact on IUD results. We selected seven materials with a wide range of properties as tracers and a single material as our base blend. The experimental results led to two major conclusions: (1) materials with different mechanical properties have dissimilar mean residence times (MRT) inside the systems and (2) blend ingredients with different mechanical properties travel at different speed inside of continuous blending systems. Results further indicated there were two critical mean residence times (MRTs): that of the tracer and that of the bulk Matching of material properties between tracers is key in order to obtain similar MRTs using a given tracer. Differences between selected tracer and bulk material properties were found to lead to differences between the bulk space time and the tracer MRT. A set of recommendations on how to select tracer materials that would help characterize accurately the RTD of a continuous flow system are presented. (C) 2018 Published by Elsevier B.V.