Effect of tableting temperature on tablet properties and dissolution behavior of heat sensitive formulations.

The tableting process involves the conversion of mechanical to thermal energy. This study evaluated the influence of temperature on the tableting behavior of formulations with different compositions. The tableting machine was equipped with a thermally controlled die to mimic the heat evolution from tableting on an industrial scale. Six formulations containing binders with a comparably low glass transition temperature were examined. Besides the polymer type and concentration, the filler was varied. Paracetamol was chosen as the model active pharmaceutical ingredient. The investigation included alterations in tabletability, disintegration and dissolution. Elevated temperatures led to an enhanced tabletability. The polymer type and concentration were decisive for the extent of alterations. The variation of the filler composition played a minor role due to the high melting points of its components. The results were confirmed in disintegration and dissolution studies. A high binding capacity and a low glass transition temperature resulted in a stronger delay of disintegration. The dissolution was sustained. Increased concentrations of the binding polymer enhanced the effect. If the tableting behavior of a formulation is changed by elevated temperatures during formulation development and production, a change of the binder type or concentration should be considered to ensure a reproducible tablet quality.

Investigating the heat sensitivity of frequently used excipients with varying particle sizes.

During tablet manufacturing an increase in the production temperature can lead to an alteration of tablet characteristics. In the present study, the influence of the initial particle size on the tableting behavior of ductile polymers upon temperature rise was investigated. Different grades of the respective materials were tableted at temperatures ranging from 22 to 70 °C. Alterations in tableting behavior were affected by the initial particle size. Smaller particle sizes led to a more pronounced decrease in yield pressure and net work of compaction during compressibility analysis. The results were confirmed in the tabletability studies. Tablets from binary mixtures with lactose containing smaller polymer particles yielded a stronger increase in tensile strength. Differences in the tensile strength increase of two grades from the same material correlated with the ratio of their median particle sizes. The alteration of compactibility profiles was also particle size dependent. The increase in solid fraction was more prominent for binary mixtures containing polymers with smaller particle sizes. However, the ratio of the median particle sizes of the compared grades showed no systematic effect. The results underline the importance of controlling the structural properties of a material carefully during formulation development and production. If a formulation responds to temperature variations, an increase in particle size might be beneficial to decrease its heat sensitivity.

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

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.

Influence of temperature on the compression behavior of pharmaceutical excipients.

Tableting on an industrial scale is characterized by an increase in temperature, which is dependent on numerous factors. The aim of this study was to examine the glass transition temperature of frequently used polymers as a critical parameter on tablet properties. Tablets were produced in a tablet press equipped with a temperature-controlled die at four different temperatures ranging from 22 to 70 °C. While pure polymers were characterized for their temperature-dependent compressibility behavior using Heckel analysis, tableting was performed from binary blends containing lactose as a filler and the polymer to be examined (ratio 9:1). Tablets were characterized in terms of tabletability, compactibility and their correlation with the glass transition temperature. The decrease in mean yield pressure upon temperature rise could clearly be correlated to the glass transition temperature of a given polymer, whereby polymers with low glass transition temperatures proved to be more responsive to temperature changes. Tablet properties were equally affected by the applied temperature despite the low polymer content. Thus, polymers with higher glass transition temperatures should be preferred in a full-production scale to avoid an alteration of tablet characteristics, whereas polymers with lower glass transition temperatures could be advantageous if a change of material properties is desired.