Contents lists available at ScienceDirect European Journal of Pharmaceutical Sciences journal homepage: www.elsevier.com/locate/ejps Understanding effects of process parameters and forced feeding on die filling Hui Ping Goh, Paul Wan Sia Heng, Celine Valeria Liew ⁎ GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore ARTICLE INFO Keywords: Die fill Forced feeding Paddle velocity Tableting process Orifice diameter ABSTRACT Die filling is a critical step during pharmaceutical tablet production and is still not well understood due to the rather complex interplay between particle attributes, die orifice diameter and fill energetics. While shoe-die filling models have been used to simulate die filling conditions, they typically lack the sophistication of the actual production-scale, feeder-based die filling conditions. The relationship between tableting process para- meters and filling into die orifices of different diameters by powders of different flowabilities requires critical examination and understanding. In this study, a special die filling contraption was designed and custom-made to simulate the effects of gravity, suction and feeder paddle assistance as present in modern rotary tablet presses. Die fill performance was studied using powders with different flow properties. Suction impact was greatest on die fill, in particular, for small orifice diameters and less permeable powders. Effect of paddle velocity on die fill was greater for compressible powders and larger orifice diameters. In comparison to suction and paddle velocity, forced feeding did not significantly affect die fill performance. Relationship between process parameters and die fill performance was found to be highly dependent on the material and orifice diameter. 1. Introduction Production of pharmaceutical tablets typically involves the three consecutive process steps of die filling, compression and tablet ejection. The die fill determines tablet weight which in turn is related to drug content and other critical quality attributes such as tablet mechanical strength, friability and disintegration. Reproducibility of die fill is hence critical as it not only affects product quality but also the overall efficiency of the tableting process (Mills and Sinka, 2013). Research in die fill was initially driven by other industries involved in powder compaction, such as powder metallurgy and ceramics (Bocchini, 1987). The die filling process can be passive (powder de- livered into a stationary die from a moving shoe) or active (powder delivered into a moving die from a stationary shoe) on the compaction system (Peeters et al., 2015; Wu, 2008). By using shoe-die models to examine the passive die fill process, interactions between powder and air during die filling could be elicited. Displacement of air from the die cavity by powder filling created a pressure gradient which opposed further powder entry into the cavity and this could be visualised by high speed video (Mills and Sinka, 2013; Wu and Cocks, 2004; Xie and Puri, 2006). Higher die fill densities achieved by the assistance of va- cuum pointed to the adverse effect of the presence of air in the die hindering its filling (Wu et al., 2003). It has been found that gravity fill of powder into a die cavity is primarily governed by three types of flow regimes: nose flow, bulk flow and intermittent flow (Mills and Sinka, 2013; Sinka et al., 2004; Wu et al., 2003; Wu and Cocks, 2004). As the feed shoe moves across the die cavity, the powder adopts a nose-shaped profile due to inertia and frictional interaction between the powder and the surface on which the shoe slides. The initial cascading of particles down the slope into the die cavity is termed as nose flow. Bulk flow occurs when powder detaches smoothly from the bottom of the powder bed into the die after the feed shoe has completely covered the die cavity. In cases where powder agglomerates detach by random into the die, the flow is termed as intermittent flow. The die fill for shoe-die model studies is usually quantified by fill ratio and feed shoe critical velocity. Fill ratio refers to the ratio between the powder mass collected in the die after one pass of the feed shoe and the powder mass in a completely filled die (Mills and Sinka, 2013). It can also be the ratio between the volume of powder collected in the die to the die volume (Wu, 2008). A higher fill ratio would mean higher fill density inside the die. The concept of critical velocity (maximum feed shoe velocity that can fill the die cavity completely with a single pass) was also used by researchers as an indicator of powder flowability and die fill performance (Mills and Sinka, 2013; Sinka et al., 2004). High fill ratio and critical velocity indicate better die fill performance. The shoe-die model was found to underestimate powder flow per- formance by half when up-scaling the data to a rotary tablet press (Schneider et al., 2007). The unaccounted suction fill effect present in rotary presses was identified subsequently through a modified shoe-die model with a movable lower punch that descended just as the feed shoe https://doi.org/10.1016/j.ejps.2018.06.026 Received 19 February 2018; Received in revised form 30 May 2018; Accepted 25 June 2018 ⁎ Corresponding author. E-mail address: phalcv@nus.edu.sg (C.V. Liew). European Journal of Pharmaceutical Sciences 122 (2018) 105–115 Available online 27 June 2018 0928-0987/ © 2018 Elsevier B.V. All rights reserved. T