Investigation of differences in mechanisms of die filling between a compaction simulator and a rotary press

Abstract

Die Filling is the critical process step in tableting as it determines the tablet weight and its variability as well as impacting tablet strength and defect propensity. Several studies have focused on modeling die filling on rotary presses, however none have investigated the matter on a compaction simulator. Therefore, the aim of this study is to characterize the die filling behavior on a compaction simulator and compare it to a laboratory scale rotary press. Special attention is paid to the complex interplay of process parameters, machine geometry and material properties. Experimental results are supported by a newly introduced physics-based calculation of the course of the exerted differential pressure as a main driver of die filling. On the compaction simulator, suction filling is shown to be more intense due to its geometry and elevated lower punch velocities, rendering paddle speed of the feed frame less crucial. On the rotary press, paddle rotation is necessary to ensure sufficient powder flow into the dies, especially at high production speed, due to a shorter filling time. An alternative fill cam geometry, where the punch is already pulled down to a certain extent before entering the feed frame, reduces the exerted suction pressure in the filling zone, giving generally lower filling yield for materials of limited flowability. The study offers a solid understanding of die filling on a compaction simulator and the underlying mechanisms. Together with the comparative experiments, the foundation for a model for rational scale transfer towards rotary presses is established.

Highlights

• first investigation of the degree of die filling on a compaction simulator.
• interplay of dynamic conditions, machine geometry and powder properties is studied.
• newly introduced numerical calculation provides insight into filling mechanisms.
• suction filling is the main driver of die filling on the compaction simulator.

Introduction

Among oral pharmaceutical dosage forms, the tablet is the most widely applied due to its low manufacturing costs and high acceptance by patients. Consequently, considerable resources are attributed to formulation and process development of tablets in the pharmaceutical industry. Especially in early formulation development, where only little material is available, compaction simulators are widely used studying the compaction, ejection and take-off behavior of formulation candidates (Desbois et al., 2019; Mazel et al., 2019; Schönfeld et al., 2024; Sun, 2015; Wang et al., 2004). However, the sub-process of die filling is only poorly understood on compaction simulators, mostly covering the impact of the feeding process on the formulation itself. Wünsch et al. studied the filling stage with regard to lubricant dispersion and the resulting drop in tablet tensile strength due to higher shearing intensity in the feed frame of the compaction simulator when compared to a rotary press (Wünsch et al., 2020). Puckhaber et al. continued this work by developing a model to predict the effect of lubricant dispersion on compressibility and compactibility (Puckhaber et al., 2024; Puckhaber et al., 2023b; Puckhaber et al., 2023a; Puckhaber et al., 2022b; Puckhaber et al., 2022a). However, the degree of die filling itself was not systematically investigated. This poor understanding is in stark contrast to the production scale, where die filling is considered the crucial step, as it not only determines tablet weight and its consistency, but also impacts tablet strength and defect propensity by over- or underfilling. If issues with die filling arise during scale up of a formulation from pilot plant to production scale, expensive trials on the respective machines have to be conducted to optimize the process conditions, the worst-case scenario being the necessity for changes to the formulation, causing significant costs due to the associated regulatory process.

To mitigate this risk, Schomberg et al. have developed a model to describe die filling under gravity filling conditions on a laboratory scale rotary press (Schomberg et al., 2023b). In gravity filling, the punch enters the filling are already pulled down (in the most drastic cases already to the lowest punch position of the fill cam before dosing out). The powder flows into the dies by means of the gravitational force, usually aided by the rotation of the paddle wheel supplying sufficient powder flow to the filling zone. The model predicts the critical paddle speed to achieve complete die filling at a given turret speed and requires only simple material properties such as the bulk density and permeability. It was consecutively extended towards production scale rotary presses, allowing for a rational scale transfer based on material and process parameters (Schomberg et al., 2023a).

Gravity filling has also been extensively studied on linear filling devices with a moving feed shoe and stationary die (Baserinia and Sinka, 2019; Schneider et al., 2007; Sinka et al., 2009; Sinka et al., 2004; Wu et al., 2003). Zakhvatayeva et al. studied gravity filling on a rotary test rig to evaluate the transferability of these results towards rotary presses (Zakhvatayeva et al., 2018). It was found that powder properties such as the cohesive strength, mass flow rate and particle size and shape have a profound impact on filling efficiency. In gravity filling, the escaping of the air from the die is of particular importance, highlighted by the fact that materials with high permeability showed the most favorable filling behavior.

However, gravity filling is employed only under special circumstances, e.g. when filling any but the first layer of a multilayer tablet. As most tablets are single layered, the usual mechanism of die filling is suction filling. When suction filling is employed, the punch enters the filling zone with the punch face being flush with the die opening. The fill cam then guides the downward motion of the punch directly under the powder bed, creating a differential pressure, the magnitude of which is determined mostly by the punch velocity and permeability of the material. Powder is actively transported into the dies by this mechanism, while simultaneously offering the benefit that only little air counteracting powder flow has to escape the die compared with gravitational filling.

The model for gravity filling was expanded towards suction filling (Schomberg et al., 2025). The fit parameters for calculating the critical paddle speed, the rotation-specific fill volume and reference volume flow were both found to correlate well with an estimated based on the lower punch velocity. The study also showed permeability to be a crucial factor, as it determines the extent of and thus, the material’s susceptibility to suction filling.

This was hypothesized earlier by Mills and Sinka, who showed that the effectiveness of suction filling increases with decreasing particle size of microcrystalline cellulose (Mills and Sinka, 2013). Several studies with a linear filling device also demonstrated the general superiority of suction filling over gravity filling, as the critical shoe velocities, representing the maximum speed of the feed shoe that still yields completely filled dies, increased significantly depending on the punch velocity (Baserinia and Sinka, 2019; Jackson et al., 2007; Mills and Sinka, 2013; Sinka et al., 2009). Zakhvatayeva et al. showed that a lactose grade of low air permeability yielded substantially lower filling efficiency under conditions of reduced suction filling, whereas materials of higher permeability gave high filling efficiencies under the same conditions (Zakhvatayeva et al., 2019).

Most of the presented studies investigated die filling and the mechanisms involved on custom testing rigs and rotary presses. To the authors’ knowledge, no published literature has ever considered the die filling behavior of pharmaceutical powders on a compaction simulator. Therefore, this study investigates the degree of die filling achieved by model excipients on a compaction simulator. For reference, comparative experiments are conducted on a laboratory scale rotary press. Multiple process setups, especially regarding fill cam geometry, are systematically studied by process parameter variation and elucidated with respect to the relevant filling mechanisms. The filling mechanisms are discussed and mechanistically complemented with physics-based calculations of the course of the differential pressure during filling.

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Materials

Anhydrous dicalcium phosphate (DCP, DI-CAFOS®-A150, Chemische Fabrik Budenheim KG, Budenheim, Germany), microcrystalline cellulose (MCC, VIVAPUR® 102, JRS Pharma GmbH & Co. KG, Rosenberg, Germany) and α-lactose monohydrate (LAC, GranuLac® 200, Meggle GmbH & Co. KG, Wasserburg, Germany) were used as model excipients of excellent, medium and poor flow behavior. DCP and LAC were lubricated with magnesium stearate (MgSt, Ligamed MF-2-V, Peter Greven GmbH & Co. KG, Bad Münstereifel, Germany) by blending in a Turbula® blender (T2F, Willy A. Bachofen AG, Muttenz, Switzerland).  The comparably long blending time was chosen as to not foster additional lubricant dispersion and changes in flow properties by the feed frame passage during the tableting experiments. As MCC requires no lubrication, none was applied to preserve its inherent flow properties. All material characterization was carried out using the lubricated materials, when applied.

Ben Kohlhaas, Jan Henrik Finke, Investigation of differences in mechanisms of die filling between a compaction simulator and a rotary press, International Journal of Pharmaceutics: X, 2025, 100405, ISSN 2590-1567, https://doi.org/10.1016/j.ijpx.2025.100405.

Read also our introduction article on Magnesium Stearate here: