Powder Characterisation Techniques for Tableting Applications

Today’s post on powder properties of relevance to specific applications focuses on one of the most widely used pharmaceutical processes: tableting. Highly stable, simple to administer, and cost-effective, tablets remain the most popular drug delivery vehicle. Tablet production has a long history but continues to evolve as the industry innovates increasingly sophisticated products and works towards greater efficiency. The drive towards continuous manufacture, faster production speeds, increasingly potent actives and the adoption of complex multi-layer tablets present modern-day tablet manufacturers with significant challenges. Understanding how to manipulate the properties of the blend towards better processing performance and products with defined critical quality attributes is essential.

The basics of tableting

The sequential stages of a tablet manufacturing process subject the powder blend to a range of different conditions. Initially, the blend is transferred from the hopper into the feedframe, from where it circulates on to the table, flowing into each die. Consecutive passes of the feedframe blades encourage complete die filling. The following “micro-process” is compression, where punches compress the prescribed volume to a defined compression force within the die to form a stable tablet. Ejection of the tablet from the die completes the process.

Moving on from traditional test methods

Historically, tablet producers have relied on powder characterisation techniques that describe a blend with just a single figure, or in terms of only one aspect of its behaviour. Carr’s Index for example, angle of repose, or even shear cell techniques have pronounced limitations when it comes to the rigorous optimisation of tableting processes and powder testing methodology has developed considerably since their introduction. Modern instruments complement automated and precise shear and bulk property measurement with dynamic testing. Dynamic analysis, of a powder in motion, is especially useful for process-related studies and for quantifying cohesion and the response of a blend to air.

Defining relevant powder properties

For tableting applications, dynamic flow properties quantify the ease with which a blend will flow into an empty or partially filled die. Furthermore, dynamic testing can detect a tendency towards segregation, of a fine, sparsely dispersed active, from the excipient bulk. Permeability can also be studied directly. Ideally, once in the die the powder blend should release air quickly to ensure a complete fill. Unreleased, entrained air may be compressed, potentially resulting in lamination or capping of the tablet, post-compaction.

Compressibility is another bulk property of relevance to the compaction step. With a highly compressible blend, tablet thickness, hardness and mechanical integrity will be compromised, whilst, for a less compressible powder the applied force from the punches will be transmitted more uniformly, giving a more homogeneous, stable tablet.

Shear cell testing does have complementary value for tableting applications and can be informative with respect to hopper discharge behaviour. Wall friction data are also helpful in predicting whether a blend is prone to ‘picking’ or adhesion of the powder to the processing equipment.

This brief analysis highlights how different powder parameters are pertinent at different stages of the process. Tools that quantify a range of behaviour characteristics for the blend, rather than measuring a single figure result, make it easier to see this ‘bigger picture’. During formulation such information promotes a more holistic approach that includes good processability as one of the criteria for success. Later, at the process design stage, these same data produce more secure understanding that can reduce the need for post-commissioning changes. And finally, during day-to-day manufacture, detailed and sensitive powder specification minimises problems surrounding batch-to-batch variability – in either the raw material or intermediate product – and supports effective troubleshooting. In all these ways an investment in the most suitable analytical instrumentation returns value at every stage in the production of a tablet.

Further reading:

1. “Choosing a Powder Tester” - https://www.freemantech.co.uk/learn/ebooks
2. “Using Powder Testing to Optimise the Processing Characteristics of Amorphous Solid Dispersions” - https://www.freemantech.co.uk/news/powder-testing-to-optimise-the-processing-characteristics-of-amorphous-solid-dispersions