Investigation on the effects of dwell time and loading strain rate on powder compaction and tablet properties: A compaction simulator study

Abstract

This study aims to decouple the effect of dwell time and strain rate on tablet strength and cracking behavior. Using a hydraulic compaction simulator, dwell time and strain rate were isolated from other parameters in the compaction cycle so that their independent contributions to tabletability could be studied. Dwell time was ranged from 10 ms – 100 s and strain rates were ranged from 1 s⁻¹ to 100 s⁻¹. Common excipients with a range of material attributes were used: microcrystalline cellulose (MCC), dibasic anhydrous calcium phosphate (DCP), and pregelatinized starch. It was found that the impact of dwell time is material-dependent and that dwell time can improve tensile strength of compacts, but only at time scales beyond what is achievable on any rotary tablet press. Moreover, only MCC tablets were observed to form cracks at high strain rates where only at extreme dwell times cracking was partially improved. When contextualized by dwell time attainable on a rotary press (10–100 ms), the effects of dwell time were found to be marginal to non-existent depending on the material. For strain rate, the effect was also material-dependent, but had a clear impact on tablet strength development and cracking behavior for MCC. Overall, it was found that for the materials tested, dwell time and strain rate can impact tabletability; however, only strain rate influences on timescales relevant for the rotary press.

Highlights

• First study which deliberately varies strain rate and dwell time independently.
• Influence on tablet properties studied for three differently deforming materials.
• Strain rate influences tableting behavior across different material classes.
• Dwell time has little to no effect on tablet properties at relevant press speeds.
• Strain rate should be the method for press scaling and not dwell time.

Introduction

A continual challenge in the pharmaceutical industry is the development of formulations and processes that produce tablets with robust mechanical strength while avoiding defects, like cracking and lamination. Two parameters that are commonly associated with tabletability are dwell time and strain rate sensitivity. Dwell time is defined as the time that the punch head flat is in contact with the compression rollers which corresponds to the minimum compression gap (e.g. punch separation) [1]. During this period, multiple mechanisms within the powder bed are reported to contribute to improved tabletability, such as stress relaxation [2], bond formation [3], and de-aeration [4]. Strain rate sensitivity (SRS), defined in the pharmaceutical literature, is defined as the difference in deformation behavior of a powder in die when compressed at two different rates [5] as shown in Eq. (1).

Eq. 1 calculates the percent difference in the inverse slope of the Heckel equation, Pyi, at two different strain rates where the higher speed test is i = 2 and the lower speed test is i = 1 [5]. This is a pragmatic way of understanding how a material’s densification changes with strain rate, but it does not measure the strength of the material after formation at different speeds. For many materials it has been shown that Py increases with the speed of compression thus indicating that the material requires higher compaction stress to achieve the same density than when compressed at a lower speed [[5], [6], [7]]. A limitation to this approach of understanding strain rate sensitivity is the analysis only considers in-die differences of a material’s deformation and not the final ejected tablet’s mechanical strength.

Many past studies have investigated the effect of strain rate and/or dwell time on the performance of excipients and formulations [[1], [2], [3],[8], [9], [10], [11], [12], [13]] while also measuring the resulting tablet’s mechanical strength, typically reported as tablet tensile strength. However, on traditional rotary presses and most single station presses, the dwell time and press speed are inherently linked. Due to this coupling, much of the previous research has been unable to study the effect of dwell time and punch velocity independently from other parameters due to equipment limitations.

Tye et al. investigated the effects of dwell time on compaction behavior of several common excipients. The authors used a compaction emulator and a hydraulic press to produce tablets with dwell times ranging from 8.1 ms to 90 s. It was found that microcrystalline cellulose showed little dependency of dwell time on tablet tensile strength whereas starch showed a significant impact of dwell time on tablet tensile strength with longer dwell times creating higher tensile strength tablets. However, in this study the speed of compaction was not decoupled from the dwell time where small dwell times also resulted in higher strain rates, thus making it difficult to determine the direct impact strain rate had on the behavior of the materials [1]. Anbalagan et al. varied punch head geometry and compression roller diameter to induce changes in temporal compression parameters and studied the impact on tablet mechanical properties while using a rotary tablet press. They found that punch head design had a marginal impact tablet strength and capping tendency. However, the speed of compression was not directly reported with changes in tooling head design. Moreover, while compression force, rate of force application, and consolidation time were kept relatively consistent in comparing punch head designs, both the dwell time and decompression times varied to a similar extent, again making it difficult to isolate the impact of each parameter on tablet mechanical strength [2].

More recently, Ouazzou et al., studied the impact of particle size distribution of maltodextrin and dwell time on tablet properties using a STYL’One compaction simulator. It was found that extended dwell times from 1 ms to 1000 ms led to less elastic recovery, increased tensile strength, and increased solid fraction. The speed of compression was kept constant between dwell times; however, the rate of unloading was different between the 1 ms and 1000 ms dwell time compaction events making it hard to determine the impact of dwell time solely on tablet properties. In addition, the authors noted that compared to compaction force and particle size distribution, dwell time had the lowest impact on tablet mechanical properties [13].

Klinzing & Troup investigated the role of air pressure in the powder bed during compression on cracking propensity of MCC tablets. In this work, the authors varied dwell time from 0 s to 100 s independently from other parameters by using a hydraulic compaction simulator and found that with sufficiently long dwell time, cracking could be avoided due to de-aeration of the tablet bed. However, the dwell times required were orders of magnitude higher than what is realistic on a rotary press [4]. While these studies more effectively isolated dwell time from other compression parameters to understand its influence on tabletability, they studied only a single material and applied different compaction profiles and methods. Therefore, further investigation into a range of different materials with a consistent method that isolates dwell time and strain rate is needed.

This study aims to leverage a single-station hydraulic compaction simulator to isolate the effects of dwell time and punch velocity to determine their individual contributions to tabletability changes and cracking behavior. The hydraulic compaction simulator allows for virtually any punch profiles to be produced and executed, providing the unique advantage of being able to vary dwell time and/or punch velocity independently from other parameters which are normally linked on a rotary press.

Three model excipients ranging from brittle to plastic materials were compressed into tablets: microcrystalline cellulose (MCC), dibasic anhydrous calcium phosphate (DCP), and pre-gelatinized starch. Of the three materials MCC and starch has been shown to be mildly visco-elastic and visco-plastic [14] whereas DCP does not show any visco-elastic properties [14,15]. Dwell time was varied between 10 ms and 100 s and strain rate of compression was varied between 1 and 100 s−1. Tabletability was measured using diametrical compression test (“tensile strength”). Visual observations and x-ray microcomputed tomography (XRCT) were used determine frequency and the extent of cracking behavior within the tablets.

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Materials

The following excipients were acquired as follows: Microcrystalline Cellulose Avicel PH-102 (DuPont™), A-Tab® Dibasic Anhydrous Calcium Phosphate (Innophos®), Starch1500 Partially Pregelatinized Maize Starch (Colorcon®), and Hyqual magnesium stearate (Mallinckrodt™), STYL’One compaction simulator, MEDELPHARM

MayLin T. Howard, Gerard R. Klinzing, Investigation on the effects of dwell time and loading strain rate on powder compaction and tablet properties: A compaction simulator study, Powder Technology, Volume 455, 2025, 120759, ISSN 0032-5910, https://doi.org/10.1016/j.powtec.2025.120759.

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