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Relaxation tests are often used in the pharmaceutical field to assess the strain rate sensitivity of pharmaceutical powders and tablets. These tests involve applying a constant strain to the powder in the die and then monitoring the stress evolution over time. Interpreting these tests is complicated because different physical phenomena, mainly viscoelasticity and viscoplasticity, occur simultaneously. These two phenomena cannot be distinguished by observing the evolution of the axial pressure alone, as it decreases in both cases. In this work, it was shown that monitoring the evolution of the die-wall pressure during relaxation can help separate the effects of these phenomena. Theoretical considerations revealed that during viscoplasticity, the die-wall pressure also decreases, whereas an increase in the die-wall pressure during relaxation indicates a viscoelastic relaxation. This was confirmed experimentally using specially designed compaction cycles on four different pharmaceutical excipients. Experimental results indicated that at low pressure, viscoplasticity was predominant, whereas at high pressure, viscoelasticity became more prominent. These results suggest that at low pressures, relaxation tests can be used to assess the viscoplastic properties of different products. However, the use of high pressure should always be avoided as viscoelastic phenomena might become more significant, and the combination of both phenomena might compromise the interpretation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Most of biopharmaceuticals, in their liquid form, are prone to instabilities during storage. In order to improve their stability, lyophilization is the most commonly used drying technique in the pharmaceutical industry. In addition, certain applications of biopharmaceutical products can be considered by oral administration and tablets are the most frequent solid pharmaceutical dosage form used for oral route. Thus, the tableting properties of freeze-dried products used as cryo and lyoprotectant could be a key element for future pharmaceutical developments and applications. In this study, we investigated the properties that might play a particular role in the specific compaction behavior of freeze-dried excipients. The tableting properties of freeze-dried trehalose, lactose and mannitol were investigated and compared to other forms of these excipients (spray-dried, commercial crystalline and commercial crystalline milled powders). The obtained results showed a specific behavior in terms of compressibility, tabletability and brittleness for the amorphous powders obtained after freeze-drying. The comparison with the other powders showed that this specific tableting behavior is linked to both the specific texture and the physical state (amorphization) of these freeze-dried powders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Capping is an important industrial problem that can arise during the manufacturing of pharmaceutical tablets. It corresponds, for biconvex tablets, to the detachment of one of the cups of the tablet during the ejection from the press or after relaxation. Solutions to this problem remain mainly empirical. Among them, precompression is widely used. One of the most popular explanation of the role of precompression in the mitigation of capping is that it increases the total time under compression. Following this interpretation, press manufacturers developped devices or machines that make it possible to maintain the pressure between precompression and main compression. In this note, we present a case study of capping. For the formulation proposed, a precompression that was maintained until the compression gave similar results as no precompression at all, i.e. capping of all the tablets. On the contrary, if the precompression was released before compression, capping stops completely. In this case, the effect of precompression is thus due to the separation of two compression events. Moreover, results prove that this separation must last long enough for the precompression to be efficient. This example shows that effect of precompression is more complex than often described in the literature., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Influence of the compaction speed on the final tablet properties is an important challenge during the scale-up of a solid dosage form. This strain rate sensitivity is generally attributed to the time dependent deformation behavior of the powder. In this work, we studied the influence of the speed on another important factor during compaction: friction between the tablet/powder and the die. An original experimental methodology was developed to study the evolution of the kinematic friction coefficient between the tablet and the die as a function of the sliding speed of the tablet on the die wall. This methodology made it possible to separate the speed used to make the tablet from the speed used to measure the friction coefficient. Results indicate that the kinematic coefficient of friction increases with the sliding speed following a logarithmic trend. This trend was observed for 4 different pharmaceutical excipients. Moreover, it was proved that the speed dependency is an intrinsic property of the friction between a tablet and a die lubricated using magnesium stearate., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

During pharmaceutical compaction, the interaction between the punch and the powder determines the formation and the aspect of the surface of the compact. In industry, the properties of the punch surface, which play a key role in this interaction, are sometimes changed by fixing an intermediate layer onto the punch to prevent sticking problems. In this article, the case of a polymer insert layer was studied. Firstly, sugar spheres were compacted with and without the polymer insert fixed onto the punches. After compaction with uncovered punches, the surface particles, which had been subjected to high deformation, were flattened on one side. However, it was observed, using confocal X-ray microfluorescence, that this kind of deformation was limited to the surface and that the bulk particles, which underwent a more isotropic deformation, still exhibited an approximately round shape. Secondly, the influence of the surface structure on the mechanical properties of the compacts was studied. The indentation hardness and the tensile strength of compacts of microcrystalline cellulose (MCC) and anhydrous calcium phosphate (aCP) were studied. No differences were found for the compacts of MCC produced with the two kinds of punches, but the compacts of aCP obtained with uncovered punches presented a higher hardness and a higher tensile strength than those obtained with covered punches., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The development of predictive models for the pharmaceutical compaction process is of great interest for not only the formulation step but also in the context of the quality by design development. This paper deals with the prediction of the compressibility, i.e. the prediction of the evolution of the density and the porosity of the compact along with the compaction pressure, both "in-die" (during the compaction) and "out-of-die (after the ejection of the compact). For this purpose, four different mixtures composed of five different pharmaceutical products were studied using a rotative press simulator. The excipients and formulations were chosen to be as near as possible to real industrial formulations. Using the volume as an additive property and a reformulation of the Kawakita equation as a function of the density, it was possible to predict the density of the compact both "in-die" and "out-of-die" with a good accuracy (residuals <3.5%). In most of the cases, for the pressure levels used in the pharmaceutical industry, the absolute error on the prediction of the porosity was below 2%. This study demonstrates that this approach could be well suited to predict the compressibility of real pharmaceutical formulations in the industrial context., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Graphical abstract Abstract Tablet final properties are mainly determined during the compaction process by the evolution of the stresses applied to the powder. Any process or product parameter that may influence this stress evolution may have a direct impact on the tablet final properties. In this article, we studied the influence of the friction between the tooling and the powder on the evolution of the die-wall pressure during compaction using flat and concave punches. Experimental studies were performed on microcrystalline cellulose as well as numerical studies using finite element method (FEM) simulation. Both methodologies indicate that increasing the friction between the powder and the tooling promotes an increase in the die-wall pressure during tableting. This is in contradiction with results that can be found in the literature. Moreover, the results of this study showed that for flat punches, the stress evolution is mainly driven by the die/powder friction. On the contrary, for concave punches, changing the punches/powder friction have also a consequence in the evolution of the die-wall pressure. This could have practical consequences in sticking situations where, due film formation on the punches, the friction between the punches and the powder may change during tableting. [ABSTRACT FROM AUTHOR]

Stress and density changes in axi-symmetric compaction of pharmaceutical powders are analysed numerically. Data measured in a compression cycle are used with a calibration procedure to assess the mechanical behaviour of powders in compaction based on a Drucker–Prager Cap model. This model is based on the elastic–plastic theory and takes into account the macroscopic characteristics of powders such as cohesion and global friction between particles. Moreover, a yield function is used to limit the admissible stresses in a tablet during a compaction cycle. This yield function depends on the first and second invariants of the stress tensor: pressure and stress deviation. To represent the plastic compaction mechanisms, a strain hardening function is used to expand the yield function with increasing volumetric strain. A finite element method coupled to the finite strain plasticity theory is used to calculate stress and strain changes in a tablet during compression and decompression. The die wall friction is estimated from the transmission effort to the lower punch with the modified equation of Shaxby and Evans. This model and the calibration procedure are applied to lactose powder. Mechanical properties calculated are compared to the experimental data measurements with a Jenike shear cell. The relative density distribution at the end of compaction and after the unloading is analysed. The normal pressure on the die is numerically estimated and analysed in terms of load transferred from powder to die during compaction and load restitution to tablet during decompression. [Copyright &y& Elsevier]

Abstract: The numerical modeling of the die compaction process using the Finite Element Method (FEM) and the Drucker Prager Cap (DPC) Model has been widely developed in recent years. The advantage of this approach is to provide access to the distribution of variables in the powder bed (local values of stresses, strains and density) which permit to understand better the process, but also to predict the influence of the tools geometry. In the field of pharmaceuticals and cosmetics only a few kinds of powder have been studied, that do not represent the variety of the powder used in this industries. In this work, we present for the first time the simulation of the compression of a cosmetic powder corresponding to an eye shadow. Moreover, one of the aims of this article was to compare the experimental results and the simulations, which was not for now widely done in the existing literature. The first step was the determination of the parameters of the powder in order to implement the DPC model for the simulation. The image of the distribution of the density and stress inside the compact during the compaction obtained by the modeling were totally consistent with the existing literature. The comparison between experimental and simulation results showed that some of the parameters were well simulated, such as the axial transmission, the radial transmission during the loading, the hardening and the final plastic deformation of the compact. Nevertheless it was also shown that there was a disagreement between experiment and simulation for the thickness under compression and the stress evolution during the unloading phase. It was proved that these disagreements came from the linear elastic model used for the simulation. This work emphasizes the importance of the comparison between experiment and simulation to improve the simulation results and prediction abilities. [Copyright &y& Elsevier]