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Introduction: Tablets are commonly produced by internally adding particulate lubricants, which are known to possibly lower the mechanical strength of tablets. This reduction is caused by the coverage of matrix forming components by lubricant particles, resulting in decreased interparticulate interactions. The known incompatibilities with some active compounds of the predominantly used lubricant, magnesium stearate, call for the in-depth characterization of alternative lubricants., Purpose: Investigation of the dispersion behavior of five commonly applied pharmaceutical lubricants by mathematically modeling the dispersion kinetics for short and extended mixing times., Methods: The dispersion behavior of five different pharmaceutical lubricants were examined by systematically varying lubricant concentration and mixing time of binary formulations and evaluating the kinetic of tensile strength reduction by theoretically estimating the surface coverage based on particle sizes., Results: For short mixing times, a unifying relationship between compactibility reduction and theoretical surface coverage was identified. Subsequently, for extended mixing times, distinct differences in the shear strength and dispersion kinetics of the investigated lubricants were found., Conclusions: The lubricant particle size controls the tensile strength reduction if short mixing times are applied. For extended mixing times, the investigated lubricants can be divided into two groups in terms of dispersion kinetics. Possible underlying reasons are discussed in detail in order to enhance the general understanding of lubricant dispersions in tablet formulations., (© 2023. The Author(s).)

Modeling of structural and mechanical tablet properties consisting of multiple components, based on a minimum of experimental data is of high interest, in order to minimize time- and cost-intensive experimental trials in the development of new tablet formulations. The majority of commonly available models use the compressibility and compactibility of constituent components and establish mixing rules between those components, in order to predict the tablet properties of formulations containing multiple components. However, their applicability is limited to single materials, which form intact tablets (e.g. lactose, cellulose) and therefore, they cannot be applied for lubricants. Lubricants are required in the majority of industrial tablet formulations and usually influence the mechanical strength of tablets. This study combines the multi-component compaction model of Reynolds et al. (2017) with a recently published lubrication model (Puckhaber et al. 2020) to describe the impact of multiple components on a formulation consisting of two diluents and a lubricant. By that, this model combination displays a meaningful extension of existing compaction models and allows the systematic prediction of properties of lubricated multi-component tablets., 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 © 2023 Elsevier B.V. All rights reserved.)

In rotary tablet presses, the powder flow into the dies is typically facilitated by paddle feeder. For internally lubricated formulations, the shear forces exerted by the paddle rotation can result in a considerable decrease in tablet strength due to the dispersion of lubricant agglomerates. Available models to describe the lubricant dispersion in paddle feeder allow only a limited quantitative description and transferability of the process. This study introduces an empirical dispersion kinetic which is able to precisely describe the reduction of compactibility due to the shear stresses inside the paddle feeder, even for inhomogeneously flowing material. Additionally, by blending different grades of magnesium stearate at three levels of lubricant concentration with two different grades of microcrystalline cellulose, the impact of bulk properties on the lubrication dispersion in the feed frame was investigated. It was shown, that for a given formulation, the kinetics of compactibility reduction are comparable for different magnesium stearate concentrations. Additionally, the bulk properties of the applied magnesium stearate grade critically affect the dispersion kinetics as well as the maximum compactibility reduction inside the feed frame. In summary, the developed model represents a meaningful extension of the currently available process models for pharmaceutical tablet lubrication., 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 © 2022 Elsevier B.V. All rights reserved.)