Evolutions of temperature and density during roll compaction of a pharmaceutical excipient.

Roll compaction is a critical unit operation in the pharmaceutical manufacture. During roll compaction, a change in the internal energy of powder due to applying of external work from the rolls can generate heat and cause an increase in the temperature of the powder, which can subsequently affect the roll compaction behaviour and the quality of ribbons. Thus, it is crucial to understand the thermal response of pharmaceutical formulations during roll compaction. This study hence aims to examine the evolution of temperature and density in powders during roll compaction. For this purpose, a systematic experimental study is performed using the peripheral quantitative computed tomography (PQCT), for the first time, and the thermographic method to investigate the thermo-mechanical behaviour of pharmaceutical powders during roll compaction. A finite element model is also developed to describe the transformation of irreversible compression work to heat as well as the energy dissipation due to the wall friction, and to predict the thermomechanical behaviour. In particular, the effect of roll speeds on the thermomechanical behaviour of powders during roll compaction is examined. It was shown that at low roll speeds, the highest temperature is reached inside of the compacted powder. As the roll speed increases, more heat is generated on the ribbon surfaces due to the powder-wall friction, while the density of ribbon deceases. It was found that the density and the temperature at the ribbon centre, were generally higher than that near to the edge, for roll compaction with fixed cheek plates.

Thermal properties of compacted pharmaceutical excipients.

Thermal properties of powders are critical material attributes that control temperature rise during tableting and roll compaction. In this study, various analytical methods were used to measure the thermal properties of widely used pharmaceutical excipients including microcrystalline cellulose (MCC) of three different grades (Avicel PH 101; Avicel PH 102 and Avicel DG), lactose and mannitol. The effect of relative density on the measured thermal properties was investigated by compressing the powders into specimen of different relative densities. Differential thermal analysis (DTA) was employed to explore endothermic or exothermic events in the temperature range endured during typical pharmaceutical manufacturing processes, such as tabletting and roll compaction. Thermogravimetric analysis (TGA) was performed to analyse the water/solvent content, either in the form as solvates or as loosely bound molecules on the particle surface. Thermal conductivity analysis (TCA) was conducted to measure thermal conductivity and volumetric heat capacity. It is shown that, for the MCC powders, almost no changes in morphology or structural changes were observed during heating to temperatures up to 200°C. An increase in relative density or temperature leads to a high thermal conductivity and the volumetric heat capacity. Among all MCC powders considered, Avicel DG showed the highest increase in thermal conductivity and the volumetric heat capacity, but this heat capacity was not sensitive to the measurement temperature. For lactose and mannitol, some endothermic events occurred during heating. The thermal conductivity increased with the increase in temperature and relative density. A model was also developed to describe the variation of the thermal conductivity and the volumetric heat capacity with the relative density and the temperature. It was shown that the empirical model can well predict the dependency of the thermal conductivity and the volumetric heat capacity on the relative density and the temperature.

An experimental investigation of temperature rise during compaction of pharmaceutical powders.

During pharmaceutical powder compaction, temperature rise in the compressed powder can affect physiochemical properties of the powder, such as thermal degradation and change in crystallinity. Thus, it is of practical importance to understand the effect of process conditions and material properties on the thermal response of pharmaceutical formulations during compaction. The aim of this study was to examine the temperature rise of pharmaceutical powders during tableting, in particular, to explore how the temperature rise depends on material properties, compression speed and tablet shape. Three grades of microcrystalline cellulose (MCC) were considered: MCC Avicel pH 101, MCC Avicel pH 102 and MCC DG. These powders were compressed using a compaction simulator at various compaction speeds (10-500mm/s). Flat faced, shallow convex and normal convex tablets were produced and temperature distributions on the surface of theses tablets upon ejection were examined using an infrared thermoviewer. It was found that an increase in the compaction speed led to an increase in the average surface temperature. A higher surface temperature was induced when the powder was compressed into a tablet with larger surface curvature. This was primarily due to the increasing degree of powder deformation (i.e. the volume reduction) and the effect of interparticule/wall friction.