Evaluation of In-Die Compression Data for a Deeper Understanding of Altered Excipient Properties upon Temperature Rise

Abstract

The thermodynamic analysis of tablet formation includes the thermal and mechanical analysis during compression. The aim of this study was to evaluate alterations of force–displacement data upon temperature rise as an indicator for changed excipient properties. The tablet press was equipped with a thermally controlled die to imitate the heat evolution from tableting on an industrial scale. Six predominantly ductile polymers with a comparably low glass transition temperature were tableted at temperatures ranging from 22-70°C. Lactose served as a brittle reference with a high melting point. The energy analysis included the net and recovery work during compression, from which the plasticity factor was calculated. The respective results were compared to the changes in compressibility obtained via Heckel analysis. Elevated temperatures reduced the necessary work for plastic deformation for the ductile polymers, which was reflected in decreasing values for the net work of compaction and the plasticity factor. The recovery work slightly increased for the maximum tableting temperature. Lactose showed no response to temperature variations. Changes in the net work of compaction showed a linear correlation to the changes in yield pressure, which could be correlated to the glass transition temperature of a material. It is therefore possible to detect material alterations directly from the compression data, if the glass transition temperature of a material is sufficiently low. Graphical Abstract

Recent Advances in Nanomechanical Measurements and Their Application for Pharmaceutical Crystals

“…[9][10][11][12]19,20,25 Even though a majority of pharmaceutical formulations are done in room temperature, the local temperature rises during tableting are often overlooked. 125 Nanoindenters equipped with high-temperature stage would be advantageous to investigate the mechanical properties as a function of temperature, which in turn provide insights for various thermally responsive solid-state phenomena such as thermosalient effects, 92,93,126 phase transitions, 127 thermal expansion, 128,129 thermal mechanochromic luminescence, 42 etc. to understand the structure−property relationship for designing temperature-sensitive smart materials.…”

“…Nanoindentation experiments on molecular materials have mostly been performed at room temperature (RT, ∼293 K). − ,,, Even though a majority of pharmaceutical formulations are done in room temperature, the local temperature rises during tableting are often overlooked . Nanoindenters equipped with high-temperature stage would be advantageous to investigate the mechanical properties as a function of temperature, which in turn provide insights for various thermally responsive solid-state phenomena such as thermosalient effects, ,, phase transitions, thermal expansion, , thermal mechanochromic luminescence, etc.…”