Preventing tablet defects through vacuum-assisted deaeration of a powder bed

Abstract

Lamination is a common defect observed during pharmaceutical tablet compression and can be attributed to air entrapment (lamination type 1) within the powder bed. In this study, a novel vacuum-inducing chamber was implemented to remove air from the powder bed prior to compaction, thereby enabling, for the first time, a systematic investigation of lamination type 1 while decoupling air entrapment from other contributing factors. Microcrystalline cellulose (MCC) was compacted on a Huxley Bertram compaction simulator equipped with a vacuum chamber under systematically varied compressive stresses, strain rates, and ambient air pressures. Consistent with established findings, reducing compressive stress and strain rate decreased the frequency and severity of lamination defects, supporting the role of process parameters in defect formation. However, when the ambient air pressure surrounding the die and punches was sufficiently reduced, lamination defects were reduced or eliminated across the range of process parameters studied. These findings provide direct experimental evidence that modulating ambient air pressure can influence lamination defects due to air entrapment in MCC tablets. Furthermore, numerical simulations of air pressure evolution upon compression showed that altering air pressure can have a greater impact on air pressure reduction than processing conditions. The novel vacuum chamber approach offers an experimental platform for studying defect formation and suggests that control of ambient pressure during compaction may represent an effective strategy for mitigating lamination type 1 during pharmaceutical tablet manufacturing.

Introduction

Lamination and capping are critical failure modes that continue to challenge pharmaceutical tablet manufacturing. The terms “capping” and “lamination” are commonly used interchangeably which leads to confusion in describing the direct factors which influence these behaviors. “Capping” can be defined as the partial or complete detachment of the tablet’s top or bottom surface from the main body which occurs mainly on convex tablets but can occur on flat faced tablets (Mazel and Tchoreloff, 2022). “Lamination”, on the other hand, can be classified into three separate categories: type 1, type 2, and type 3. As outlined by Mazel and Tchoreloff (Mazel and Tchoreloff, 2022), type 1 lamination is due to air entrapment, type 2 is due to die wall pressure and shear stresses upon ejection, and type 3 is specific to biconvex tablets where a single plane of failure occurs due to a tensile stress being generated in the center of the tablet after unloading. For the current work presented here, type 1 lamination, due to air entrapment, is the sole focus of the study.

The impact of air entrapment on compression defects has been recognized for decades. For example, Long, et al. showed that when compressing wax, an increasing volume of gas was trapped within the powder bed and was a function of increasing compaction speed, increasing die size, and decreasing particle size (Long and Alderton, 1960). Later Mann, et al. showed that the tolerance between the punch and die influenced the degree of capping (Mann et al., 1981). Work by Tanino, et al. demonstrated that compression parameters such as low speed and low pressure aided in reducing capping defects (Tanino et al., 1995). More recently, Mazel, et al. showed direct visual evidence that air entrapment can create bubbles on the surface of the tablets along with random cracks throughout the tablet band (Mazel et al., 2015a).

Numerical work describing the evolution of air pressure during compaction has been presented by Zavaliangos, et al. for a 1D compaction scenario (Zavaliangos et al., 2017). This work showed higher starting powder relative density (RD) can decrease the degree of entrapped air when compaction occurs to the same final RD. Moreover, evaluation of the influence of punch velocity and final compaction RD showed that high speeds and higher final RD both increase the degree of entrapped air. Building on the 1D work of Zavaliangos, et al., Klinzing and Troup expanded to a 2D axisymmetric geometry while including a coupling to FEM models of compaction to capture the influence of density gradients upon compaction, thus resolving the gradients of air pressure throughout the tablet upon consolidation (Klinzing and Troup, 2019). In addition, this work further emphasized the impact of punch velocity on entrapped air and examined the impact dwell time had on relieving air pressure. Furthermore, experimental results indicated that regions of high air pressure toward the surface of the tablet corresponded with regions of damage within the tablet as imaged through x-ray microcomputed tomography (XRCT). It was also found that a dwell time of 100 s was required to eliminate lamination type 1 defects from a tablet.

As discussed in the literature previously, mechanisms to eliminate lamination type 1, cracking due to air entrapment, can be accomplished through the reduction of compression speed, compression pressure, granulation level, or changing excipient grades, and thickness of the tablet in-die (Garr and Rubinstein, 1991, Long and Alderton, 1960, Mazel et al., 2015a, Ruegger and Çelick, 2000, Tanino et al., 1995) However, the influence of atmospheric conditions on the occurrence of type 1 lamination in pharmaceutical tablets has not yet been explored. Outside of the pharmaceutical industry, the use of vacuum to aid in compaction is known. Studies have shown that powder compaction with the assistance of vacuum results in improved material properties and processing (Jiménez et al., 2009, Khaimook and Chai, 2019, Lee et al., 2008, Wang et al., 2022). Consequently, the present study aims to comprehensively evaluate the impact compaction parameters have on type 1 lamination with the use of a novel vacuum attachment that induces a vacuum environment around the die and punches during high-speed compression. This setup isolates the impact of air entrapment from other parameters and makes it possible to systematically evaluate the individual contributions of compaction speed and stress on tablet defect occurrence. By minimizing the contribution of air entrapment during compaction, this work seeks to advance the understanding of lamination type 1 through experimental evaluation of a processing space and numerical simulations of air pressure. The results of this study are intended to guide potential processing controls, support operational troubleshooting, and inform further formulation development measures to reduce tablet defect formation.

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Materials

A single model material system was utilized throughout the study: microcrystalline cellulose (Avicel® PH-102 NF, Roquette) internally lubricated with magnesium stearate (HyQual 5712, Mallinckrodt).

Magnesium stearate was screened through a #60 mesh sieve (250 μm) and then added at a 2 % mass ratio to the microcrystalline cellulose. Blending was conducted using a Turbula blender (WAB US Corp.) for a total of 138–147 revolutions to produce the lubricated blend.

Klara Thiele, Ewelina Randall, Gerard R. Klinzing, MayLin Howard, Preventing tablet defects through vacuum-assisted deaeration of a powder bed, International Journal of Pharmaceutics, Volume 701, 2026, 127147, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2026.127147.

Read also our introduction article on Microcrystalline Cellulose here: