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.

A novel use of friability testing for characterising ribbon milling behaviour.

Dry granulation using roll compaction (DGRC) has been increasingly adopted in the pharmaceutical industry due to its unique advantage of not requiring liquid binder and a subsequent drying process. However the DGRC process presents also some challenges, in particular, a high fine fraction generated during the milling stage significantly limits its application. Although the fines produced can be recycled in practice, it may lead to poor content uniformity of the final product. At present there is a lack of mechanistic understanding of milling of roll compacted ribbons. For instance, it is not clear how fines are generated, what are the dominant mechanisms and controlling attributes and whether any measurement technique can be used to characterise ribbon milling behaviour. Therefore, the aim of this paper was to assess whether ribbon milling behaviour can be assessed using some characterisation methods. For this purpose, friability was evaluated for ribbons made of microcrystalline cellulose (MCC) powders using a friability tester that was originally developed for characterising the tendency of pharmaceutical tablets to generate small pieces while being abraded. Granules were also produced by milling of the ribbons and their size distributions were measured. The correlation between the fine fraction of the granules with ribbon friability was then explored. It was found that there was a strong correlation between ribbon friability and the fine fraction of granules generated during milling. This implies that friability tests can be performed to characterise ribbon milling behaviour, and ribbon friability provides a good indication of the fraction of fines generated during ribbon milling.

The application of terahertz pulsed imaging in characterising density distribution of roll-compacted ribbons.

Roll compaction is a commonly used dry granulation process in pharmaceutical, fine chemical and agrochemical industries for materials sensitive to heat or moisture. The ribbon density distribution plays an important role in controlling properties of granules (e.g. granule size distribution, porosity and strength). Accurate characterisation of ribbon density distribution is critical in process control and quality assurance. The terahertz imaging system has a great application potential in achieving this as the terahertz radiation has the ability to penetrate most of the pharmaceutical excipients and the refractive index reflects variations in density and chemical compositions. The aim of this study is to explore whether terahertz pulse imaging is a feasible technique for quantifying ribbon density distribution. Ribbons were made of two grades of microcrystalline cellulose (MCC), Avicel PH102 and DG, using a roll compactor at various process conditions and the ribbon density variation was investigated using terahertz imaging and section methods. The density variations obtained from both methods were compared to explore the reliability and accuracy of the terahertz imaging system. An average refractive index is calculated from the refractive index values in the frequency range between 0.5 and 1.5THz. It is shown that the refractive index gradually decreases from the middle of the ribbon towards to the edges. Variations of density distribution across the width of the ribbons are also obtained using both the section method and the terahertz imaging system. It is found that the terahertz imaging results are in excellent agreement with that obtained using the section method, demonstrating that terahertz imaging is a feasible and rapid tool to characterise ribbon density distributions.