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.