(725d) Influence of the Rheology of Lactose Excipients on the Feeding Consistency in Tabletting Processes

Minimizing the variability in the feeding process is a crucial challenge in oral delivery systems (e.g. tabletting, capsule filling) to ensure good quality and consistency of the end product. To control and reduce the variability in the feeding rate, it is important to characterize the material properties and bulk behaviour of the powder. It is known that good flowing properties of pharmaceutical powders are required to achieve uniform flow into the die cavities. Insufficient flow can lead to uneven filling of the dies, resulting in large weight and dosage variations of the final tablets. Moreover, at high tableting speeds, the time to fill dies is reduced, making flow properties of the blend even more important.

Lactose is one of the most widely used excipients in the pharmaceutical industry. There are many reasons for its popularity, such as the fact that lactose is largely inert, relatively inexpensive, safe, available in many different grades, and has a long history of usage in successful formulations world-wide. For direct compression processes like tableting, lactose excipients can be used as a filler-binder to provide bulk density, compaction, and flow to the formulation.

In this study, the rheological properties of lactose powders have been investigated with the rotating drum method (GranuDrum) and correlated with the actual consistency of flow achieved in a tableting system. The investigation of powder flowability at different drum rotating speeds gives useful information on the evolution of powder processability at higher shear rate. Indeed, with the historical repose angle characterization method, the stress state at which the powder is submitted is far from the conditions encountered in a tableting machine. In this work, we observed that some excipient grades exhibit shear-thinning behaviour (i.e. an increase of flowability with increasing applied stress) while others show the opposite (i.e. a shear-thickening behaviour). The classification of powder cohesiveness is therefore inverted at high shear. These observations have been correlated with the mass variation of tablets produced with a RoTab tableting press at different feeder speeds. We present the correlation between the flowability assessments obtained with the rotating drum and the weight consistency of the produced tablets. We thus highlight the importance of powder characterization at a stress state equivalent to those at which the powder is processed.