Quantitative assessment of the influence of tapered dies and compaction position on the propensity of lamination due to air entrapment during pharmaceutical compression

Abstract

Air entrapment is a primary cause of tablet lamination, yet the quantitative impact of specific tooling variables remains underexplored. This study investigates the influence of tapered dies and compaction position on lamination type 1 using two distinct formulations: a plastic MCC -based blend (FMCC) and a brittle Mannitol-based blend (FMann). Tablets were manufactured using a compaction simulator mimicking high-speed rotary press kinematics, varying die geometry (straight vs. tapered), punch-die clearance, and compression position. Lamination propensity was quantified by identifying the compression pressure threshold at which defects occurred, which is termed lamination pressure.

Results demonstrated that facilitating air escape, either through increased clearance or by compressing higher in the die, increased the lamination pressure. While the tooling effects were limited for the plastic formulation, the brittle formulation showed significant sensitivity to these parameters. Notably, compressing high in the die was found to be more effective than using a tapered die, as tapered dies offered no additional benefit when the compression position was already optimized. Results indicate that optimizing compression position is an industrially more significant solution for air entrapment than the use of tapered dies.

Introduction

Tableting is one of the most common processes in the pharmaceutical industry. At the industrial scale it is generally performed using large rotary presses that are capable of producing up to 1 million of tablets per hour. At these high production rates, the compression event can be as short as a few tens of milliseconds. While these high speeds enable significant throughput, they are also known to cause tablet defects in some cases. Two of the most common defects are capping and lamination. Both involve breakage in a plane perpendicular to the compaction direction; however, capping corresponds to a failure of the top or bottom of the tablet (e.g. the cup in the case of biconvex tablet) whereas lamination corresponds to a failure in the tablet band1. Unfortunately, these defects are often conflated in the literature, making it difficult to discern which defect was actually studied.

Air entrapment is the most frequently cited reason for tablet defects. It has been proven to cause lamination in the case of lamination type 1,2, 3, 4 but there is currently no proof in the literature that it is involved in capping.5 Nevertheless, several publications regarding air entrapment refer to the studied defects as capping. 6,7 Although it is difficult to characterize defects without photographic evidence, in some cases, defects labeled as capping are clearly lamination.8 Note that other lamination types were also described.4 type 2 corresponds to lamination due to shear stress during the ejection whereas lamination type 3 occurs due to tensile stress appearing in the center of the tablet specifically in the case of convex tablets. Neither of these two lamination types involves air entrapment. In the present work, we focus on the case of lamination type 1 and assume that previous studies linking air entrapment to tablet defects were investigating lamination type 1, even if termed capping.

It is well known that lamination type 1 is influenced by process parameters like compression speed or precompression pressure for example.4,9,10 Essentially, any parameter that facilitates air escape from the die may reduce lamination occurrence. For example, Mann et al. showed that increasing the punch die clearance increased the lamination pressure (referring to the defect as capping).6 This point was also studied using numerical modelling leading to conflicting results. Kremer11 found that the clearance between the punch and the die had a minor importance. On the contrary Zavaliangos et al.7 found that the clearance was a key factor for the increase of interstitial air pressure.

While altering punch and die clearance is challenging and may promote flashing,12 and is as such not really a realistic industrial solution, a related solution is the use of a tapered die. Tapered dies are generally considered helpful for releasing air from the formulation,13 a point confirmed numerically.7 Nevertheless, from an experimental point of view, if tapered dies were found useful to release the die wall pressure and the friction, reducing microcracking14 or lamination type 2,4 their effect on lamination type 1 was not found obvious.4

Finally, another variable which is often considered regarding lamination is the upper punch penetration which determines the compression position in the die.13 Nevertheless, no papers could be found in the literature about the relation between this parameter and lamination type 1.

As no experimental work currently exists on the impact of tapered dies and upper punch penetration on lamination due to air entrapment, we propose a quantitative study of these two variables. To better interpret the results, a case with a large clearance between the upper punch and the die was also studied.

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Material and methods

Powders

Two powder formulations were investigated in this study, selected based on prior trials and in-house expertise. The excipients used included Microcrystalline Cellulose (MCC PH 200, Dupont, USA), spray-dried Mannitol, (Pearlitol® 100SD, Roquette, Lestrem, France), Pregelatinized Starch 1500G (Colorcon, Pennsylvania, USA), and Magnesium Stearate (Ligamed MF-2-V, Peter Greven, Bad Münstereifel, 138 Nordrhein-Westfalen, Germany). Each formulation was prepared by blending 300 g of powder in a 1.2 L container.

The first formulation, referred to as FMCC, consisted of 98% MCC PH 200 and 2% Magnesium Stearate. The second formulation, referred to as FMann, comprised 88% Pearlitol® 100SD, 10% Pregelatinized Starch 1500G, and 2% Magnesium Stearate. Blending was performed for 5 minutes at 49 rpm using a Turbula® mixer (model T2C, Willy A. Bachofen AG, Muttenz, Switzerland). The bulk density of the formulations was 0.42 g.cm-3 for FMCC and 0.58 g.cm-3 for FMan, which resulted in an occupancy of the container during blending of 60% for FMCC and 43% for FMan.

After blending, formulations were stored at 38 – 43% relative humidity at 22 – 25 °C for a minimum of 24 hours prior to tableting.

Tablet manufacturing

Tablets were manufactured using a compaction simulator (Styl’One Evolution, MEDELPHARM, Beynost, France), a single-station, instrumented tablet press equipped with strain gauge-based force sensors and incremental position sensors on both punches. The simulator features independently driven motors for each punch, allowing precise punch motion control.

Tablets were manufactured using Euro B punches. Three punches were used: 11.28 mm round flat upper punch, 11.28 mm round flat lower punch and 11 mm round flat upper punch. Two 11.28 mm round dies from ACM (Avilly-Saint-Léonard, France) were used: a straight die and a tapered die with a taper depth of 4.76 mm, a total diameter enlargement of 0.08 mm and a taper angle around 0.3°. A drawing of the dies is given in supplementary materials S1. Three combinations were selected (Table 1). The 11 × 11.28S configuration was used to confirm the impact of the clearance described in the literature,6 providing a clearance around 170 µm compared to around 30 µm with the 11.28 × 11.28S configuration. The upper punches had no undercut, ensuring constant clearance along the punch tip.

Charbel Madi, Johny Bertels, Vincent Mazel, Quantitative assessment of the influence of tapered dies and compaction position on the propensity of lamination due to air entrapment during pharmaceutical compression, Journal of Pharmaceutical Sciences, 2026, 104412, ISSN 0022-3549, https://doi.org/10.1016/j.xphs.2026.104412.