Effect of material properties on the residence time distribution (RTD) of a tablet press feed frame

In continuous manufacturing (CM) of pharmaceutical tablets, the residence time distribution (RTD) of the tablet press feed frame plays an important role in ensuring the critical quality attributes (CQAs) of the final product. Knowledge of factors affecting the RTD of the feed frame is necessary for sufficient RTD model development. The aim of this work is to investigate the effect of material properties on the mean residence time (MRT) and the lag time. Seven materials with different powder properties were used and the tracer concentration as a function of time were obtained. The RTD model obtained by tracer experiments is approximated using a plug flow reactor (PFR) and a continuous stirred tank reactor (CSTR). The loading plots of principle component analysis (PCA) indicated that the powder bulk density is correlated with the RTD model parameters. Therefore, we focus on establishing the relationship between the bulk density and the MRT. As a result, a linear correlation is obtained to describe the relation between the MRT and the powder bulk density. The simulated results show that the material with lower bulk density had higher risk of producing out-of-specification (OOS) products in comparison to higher bulk density powders.