Parameter-dependent stress states and their effects on properties of press-coated tablets

Abstract

Press-coated tablets (PCTs) are a modern dosage form designed to circumvent the negative effects of liquid and heat exposure that may damage drug substances during common wet coating processes for tablets. However, the production process is complex and the mechanical properties of the formulations of the different compartments may lead to challenges regarding processability, distribution of properties, and mechanical stability of the PCTs. In this study, materials with markedly different deformation properties were combined to elucidate the stress distribution during press coating and to assess the effects of process parameters and core geometry on the final PCT properties. Thorough structural investigations of all PCT compartments and the in-die analyses of axial and radial stress were applied. The simplistic approach to unify effects on the core properties by relating the punch force only on the projection area of the core only applies to the recovered core diameter and fails for further parameters. It accordingly requires more consideration of the complex stress states. The radial stress analyses clarify the anisotropy within the compression process of PCTs. It explains the findings on the distributions of porosity across different coat compartments and on the compactibilities of the recovered core. Finally, the breaking pattern of PCTs were explained with structural findings and the deduction of acting residual stresses.

Introduction

The press-coating of tablets is an alternative to classical wet coating if the latter is inapplicable due to the material’s susceptibility towards hydrolysis or heat exposure. In this approach, a drug-containing core tablet is compacted a second time inside a powder blend, which forms the coat (Kaljević et al., 2016). In addition to functional coatings (Lin and Kawashima, 2012), this process opens the possibility to combine different drugs or different release profiles in the coat and core compartments (Latha et al., 2011; Lin et al., 2004; Picart et al., 2022b). However, the production process of such press-coated tablets is complex (Rujivipat, 2010), as the state of the core before coating, as well as the process parameters during coat compression, interact to influence the final tablet properties. Based on its complex structure, different volumes of the final tablet must be differentiated, at least the core, the top and bottom layer of the coat and the outer annulus of the coat (Picart et al., 2021). In all these, the determining structural parameter, porosity, may be different compared to a mono tablet (Ascani et al., 2019; Diarra et al., 2015; Sinka, 2007) based on the deformation behaviour and process history of the components. Accordingly, application properties such as mechanical strength, disintegration, and dissolution may be altered.

The elastic recovery of different materials influences the tendency of the tablet to delaminate during and after the ejection (Mazel et al., 2013; Vaithiyalingam and Sayeed, 2010). A large difference in the elastic recovery of core and coating materials may lead to defects in the tablet structure. Cores with high elasticity cause delamination of PCTs made using a coat material with lower recovery. The increased expansion of the core causes stress that the core exerts on the coat. If this stress exceeds the bonding strength of the coat, cracks develop in the coat, eventually leading to delamination. However, even PCTs made using a combination of coating materials with high elastic recovery and core materials with low elastic recovery may lead to structural defects in the tablet. This is described by the effect of the expanding coat on the core. Cores with low strength exhibited cracking under this applied stress (Nguyen et al., 2020).

The measurement of the die wall stress and the related assessment of the axial-radial stress distribution have already been applied to compression processes of excipients, drug substances, and formulations (Abdel-Hamid and Betz, 2011; Michrafy et al., 2009; Obiorah, 1978; Windheuser et al., 1963). It was, inter alia, applied to identify the inverse correlation between crystal hardness and radial stress transmission (Higuchi et al., 1965) and to establish an easy method for assessing material plasticity without determining the material’s true density, which is often challenging (Vreeman and Sun, 2022). The literature attributes different stress transfer patterns to materials exhibiting plastic deformation behaviour and to materials exhibiting brittle fracture behaviour during deformation (Carstensen and Toure, 1980; Cocolas and Lordi, 1993). For the analysis of press-coated tablets, Picart et al. applied the die stress analysis for the first time to elucidate the effect of the punch shape on the coating process (Picart et al., 2022c).

In this study, the effects of core and coating compression stress, as well as core diameter, on the structural properties of press-coated tablets and their separate compartments were investigated. Based on the differences in porosity across the compartments, the measured stress state and distribution during compression (axial and radial stresses), the mechanical strength, as well as the tablet fractioning pattern and the residual stresses within the final PCT, were deduced. In particular, our results concerning the porosity distribution and the formation of various fracture profiles are compared with the work of Picart et al. (Picart et al., 2022a; Picart et al., 2021) to extend their findings to new material combinations and deepen the analysis of axial-radial stress distribution.

The effects of anisotropic stress state during coat compression on core properties were investigated using radial strength measurements. The core was analysed after coat compression to assess geometric changes (height and diameter), resulting core porosities, and core tensile strengths. These changes in the DCP cores were compared with the results of changes in lactose and MCC cores from the work of Picart et al. (Picart et al., 2021).The altered physical core properties were compared with the results of other experiments involving complex compression (Carstensen et al., 1985; Meng et al., 2021; Pengjin et al., 2024) and decompression processes (Mazel et al., 2024; Radojevic et al., 2021).

To understand the influence of processing parameters in the complex manufacturing process of press-coated tablets (PCTs), the structure and mechanical properties were investigated in depth. The effects observed at the whole PCT level are traced to structural differences in the coat and core compartments, depending on process conditions and the geometry of the tablet core. To explain these, stress distributions and their effects are taken into account, and the overall effects on breakage patterns on the PCTs are elucidated.

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Materials

Microcrystalline Cellulose (MCC, Vivapur® 102) and dicalcium phosphate (DCP, Emcompress® anhydrous; both JRS Pharma, Rosenberg, Germany) were used as common excipients with drastically different particle deformation properties. Magnesium stearate (MgSt, Carl Roth, Karlsruhe, Germany) was used as a lubricant and colloidal silica (CS, Aerosil® 200, Evonik, Essen, Germany) was used as a flow aid.

Henry Brauns, Chi Ki Leung, Jasper N. Ward-Berry, J. Axel Zeitler, Jan Henrik Finke, Parameter-dependent stress states and their effects on properties of press-coated tablets, International Journal of Pharmaceutics: X, Volume 12, 2026, 100610, ISSN 2590-1567, https://doi.org/10.1016/j.ijpx.2026.100610.

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