Powder flow in a tablet press: Comparison of coarse needle-shaped vs. micronized API formulations

Abstract

This study explores the often-overlooked relationship between API particle morphology and large-scale feeding dynamics in rotary tablet presses. Using coarse needle-shaped and micronized Acetaminophen (APAP) as model APIs, we examined how particle size and shape influence powder flow and tablet weight uniformity. Blends were characterized at a small scale for flowability, wall friction, density, and permeability to establish predictive links to press performance.

Tableting experiments revealed that the hopper–feeder–die system plays a critical role in weight consistency. Rathole formation was particularly prevalent in coarse APAP blends, leading to severe flow disruptions and increased tablet weight variability, whereas micronized blends formed unstable ratholes that did not impair flow continuity. At the feeder–die interface, permeability emerged as a key determinant of die-filling efficiency by enhancing the suction effect. High paddle speeds mitigated variability, while turret speed mainly influenced tablet weight without impacting variability. Interestingly, blends with lower permeability exhibited superior die-filling efficiency, challenging conventional assumptions based on flow indices alone. Paddle geometry further influenced outcomes; designs with more spokes and larger hubs increased variability under low-speed conditions.

By integrating particle-scale characterization with process-scale observations, this work introduces a framework for predicting performance beyond traditional flow metrics, highlighting how matched flowability does not guarantee equivalent tableting behavior. These insights advance a material-informed approach to formulation and process design, reducing reliance on empirical optimization.

Introduction

Tablets are among the most widely used drug delivery systems in the pharmaceutical industry, valued for their cost-effective manufacturing, patient compliance, precise dosing, and stable chemical and physical properties [[1], [2], [3]]. They are mass-produced by compressing granular powder on high-speed rotary presses. From a powder flow perspective, a rotary tablet press consists of three key components: (i) a feed hopper that stores the powder before compression, (ii) a paddle feeder that transfers the powder from the hopper into the tablet die, and (iii) a rotating turret that holds the tablet dies, where upper and lower punches compress the powder before being ejected as a finished tablet [[3], [4], [5]].

The flow behavior of a pharmaceutical blend within a tablet press is often influenced by the particle size and shape of the active pharmaceutical ingredient (API). Understanding this flow is crucial for developing a robust manufacturing process. Additionally, material-sparing flow characterization experiments can provide valuable insights, reducing the need for extensive full-scale tablet press trials. Besides material-sparing small-scale experiments, evaluations at the pilot scale are equally critical. They provide a realistic picture of the practical challenges encountered in industrial tablet press operations, serving as a bridge between fundamental characterization and commercial-scale manufacturing.

While significant attention has been given to the die-filling mechanism, the impact of powder flow behavior within the tablet press hopper on die-filling has received comparatively less focus. Due to space constraints, most tablet presses utilize asymmetric or eccentric hopper designs [6]. Unlike symmetric hoppers, where Jenike’s theory can predict powder flow behavior, flow predictions in eccentric hoppers require first-principles numerical techniques such as the Discrete Element Method [6,7] and performing actual experiments.

Eccentric hoppers generally exhibit higher discharge rates than conical hoppers but are more prone to funnel flow and require a steeper inclination to achieve mass flow [8]. In a tablet press, the hopper outlet connects to the feeder, where a rotating paddle controls powder dispensation. This rotating paddle induces preferential powder flow within the hopper, further complicating the dynamics at the hopper-feeder interface [5,9,10]. Any fluctuations in hopper flow can directly influence the consistency of powder delivery from the feeder into the die cavity. Therefore, evaluating powder flow from the hopper to the feeder is essential for optimizing the tableting process and ensuring uniform die-filling.

The final step before tablet compression is die-filling, where powder flows from the feeder into the die cavity. Tablet quality depends directly on die-filling consistency, making it a critical, rate-limiting factor in tablet production [11,12]. High variability in die-filling can compromise tablet quality and, in severe cases, lead to batch rejections. Typically, a tablet weight variability of less than 1 % (w/w) is desired [13].

For a given powder, die-filling efficiency is primarily governed by process parameters such as feeder paddle speed and die turret speed. Increasing paddle speed enhances powder bulk density over the dies, thereby increasing the filled powder weight [3,9,11,14,15]. Beyond paddle speed, paddle design and the number of spokes also influence die-filling and should be carefully considered [10,[16], [17], [18]]. While increasing turret speed can improve tablet production rates, it reduces the die residence time under the feeder, thereby decreasing die-filling efficiency and consistency [15].

Powder flows into the die due to gravity [14,19] and forced feeding, which is further assisted by the suction pressure generated by the rapid downward movement of the lower punch at the overfilling cam [4,20,21]. Several factors—including die size, powder properties, and turret speed affect suction pressure and die-filling efficiency [[21], [22], [23], [24]]. The suction effect is more pronounced with smaller die sizes and powders with low permeability. Additionally, local densification and particle interlocking further contribute to improved die-filling efficiency.

In a pharmaceutical tablet blend, the active pharmaceutical ingredient (API) is often the most cohesive component, playing a critical role in powder flow behavior [25,26]. The particle size and shape of the API are key considerations in the design and development of tablet formulations [27,28]. Generally, larger, more spherical particles exhibit better flowability than smaller or irregularly shaped ones [[29], [30], [31]]. For instance, acetaminophen (APAP) round crystals flow more efficiently than their irregular counterparts [32,33].
API crystals are frequently needle-shaped, which hinders powder flow due to increased particle interlocking. In some cases, these needle-shaped crystals have to be micronized to enhance bioavailability. However, the resulting smaller particles experience stronger cohesive van der Waals forces, further reducing flowability. Studies have shown that powders with finer particle sizes can exhibit intermittent die-filling behavior, leading to inconsistencies in tablet production [34].

While the influence of API size and shape on powder flowability has been studied in isolation, its impact on the complex dynamics of tablet manufacturing remains less explored. In practice, upstream variations in powder flow can significantly affect the quality of the final drug product. Additionally, most previous research has focused on the individual effects of excipients, despite pharmaceutical formulations being a blend of both APIs and excipients. Therefore, studying their interactions collectively is essential to gaining a more comprehensive understanding of their combined influence on powder flow and overall manufacturability.

In the early stages of pharmaceutical development, API is expensive, making large-scale manufacturing experiments impractical. As a result, small-scale, material-sparing flow experiments, such as those using ring shear testers, rheometers, and other analytical tools, are essential for gaining insights into powder flow behavior in tablet presses. Previous studies have investigated die-filling behavior using parameters such as the flow function coefficient, wall friction, permeability, bulk density, and angle of repose [15,22,35,36]. While most of these studies utilized linear or rotary die-filling simulators, relatively few have focused on actual rotary tablet press systems.

Flowability properties play different roles depending on the die-filling mechanism. Static flowability properties, such as the angle of repose and compressibility, are more relevant for gravity-driven die-filling, whereas dynamic flow properties become more critical in forced-feeding systems. A poorly flowing blend can increase tablet weight variability across different tablet presses, leading to process inefficiencies and quality concerns [13]. Powders with higher permeability primarily rely on gravity for filling, while those with lower permeability are influenced more by suction effects [4,37]. Nevertheless, having higher permeability is generally beneficial, as it leads to quick removal of entrapped air irrespective of the filling mechanism.

Despite extensive research on powder flow and die-filling, the correlation between powder properties and flow behavior from the hopper into the feeder has received limited attention. This study aims to bridge that gap by evaluating the feasibility of small-scale flow property predictions for full-scale manufacturing. By identifying trends between material-sparing experiments and large-scale processing, this research seeks to enhance the efficiency and reliability of pharmaceutical powder evaluation.

This study evaluated powder flow behavior in a pilot-scale KORSCH XL 100 rotary tablet press using pharmaceutically relevant blends of microcrystalline cellulose, lactose, and two grades of acetaminophen (APAP): coarse needle-shaped and micronized. Blends were formulated to have comparable flow function coefficients by adjusting APAP content, enabling a controlled comparison of particle morphology effects. Key powder properties, such as flow function coefficient, wall friction, permeability, and bulk density, were measured using small-scale, material-sparing tools. Tablet production was assessed under three scenarios: manual overfilling, automatic mode with varying paddle/turret speeds, and paddle design changes. Hopper-to-feeder flow was visually observed, and die-filling performance was assessed via tablet weight variability.

While most prior studies used single-component model powders or excipients in small-scale feed-frame simulators, this work employed pharmaceutically relevant blends in a pilot-scale tablet press, providing more industrially applicable insights. Especially comparing the commonly utilized API particle shapes and sizes (needle-shaped and micronized), which may have similar flow properties, but can behave differently in a tablet press. Additionally, this study links the flow of powder in the hopper simultaneously with the tableting operation and assesses its impact on tablet weight variability, which has previously been ignored. This study illustrated the application of the Quality by Design (QbD) framework described in ICH Q8. By linking the critical material attributes with critical process parameters, it evaluates the combined influence on tablet critical attributes.

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Rohit Kumar, Matthew K. Longtin, Jonathan V. Cummings, Bhavin Parekh, Mark A. Oliveira, Raghu V.G. Peddapatla, Renato A. Chiarella, Powder flow in a tablet press: Comparison of coarse needle-shaped vs. micronized API formulations, Journal of Drug Delivery Science and Technology, Volume 115, Part 2, 2026, 107804, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2025.107804.