Powder Characterization Techniques for Tableting Applications
Simple to administer, tablets are a feature of everyday life. Tablet production has a history dating back more than a century, but retains its ability to frustrate. The drive towards faster production speeds, increasingly potent actives and the adoption of complex tablet structures present modern-day tablet manufacturers with significant challenges. Understanding how to manipulate the properties of the blend towards better processing performance and high quality of final product is essential.
The sequential stages of a tablet manufacturing process subject the powder blend to range of different conditions. Initially, the blend has to be transferred from the hopper into the feedframe, from where it is circulated on the table in order that it flows into the die. Consecutive passes of the feedframe blades encourages the powder to completely fill the die. The following “micro-process” is compression, where punches compress the prescribed volume to a defined depth within the die in order to form a stable tablet. Ejection of the tablet from the die then completes the process.
Historically, tablet producers have relied on powder characterization techniques that describe a blend with just a single figure, or in terms of only one aspect of its behavior. Carr’s Index for example, a bulk property based measure, or shear cell analysis. However, over the last decade powder testing methodology has developed considerably. Modern instruments such as the FT4 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.
For tableting applications, dynamic flow properties quantify the ease with which a blend will flow into an empty or partially filled die. And indeed, the likelihood of 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 will be compressed, potentially resulting in lamination or capping post-compaction.
Compressibility is another bulk property of relevance during 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 efficiently, giving a more homogeneous, stable tablet. Shear and wall friction data are also useful 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 provide a range of behaviour characteristics for the blend, rather than just 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, this same data produces more secure understanding that can reduce the need for post-commissioning changes. And finally, during day-to-day manufacture, detailed and sensitive powder specification minimizes problems surrounding batch-to-batch variability – in either the raw material or intermediate product – and supports better troubleshooting.
In all these ways an initial investment in the most suitable analytical instrumentation returns value at every stage in the life of tablet, securing a good powder-plant fit and delivering the very best long-term performance. Giving powder measurement the attention it merits pays significant dividends.
Tim Freeman, Managing Director, Freeman Technology
Tim Freeman is Managing Director of powder characterisation company Freeman Technology for whom he has worked since the late 1990s. He was instrumental in the design and continuing development of the FT4 Powder Rheometer® and the Uniaxial Powder Tester. Through his work with various professional bodies, and involvement in industry initiatives, Tim is an established contributor to wider developments in powder processing.
Tim has a degree in Mechatronics from the University of Sussex in the UK. He is a mentor on a number of project groups for the Engineering Research Center for Structured Organic Particulate Systems in the US and a frequent contributor to industry conferences in the area of powder characterisation and processing. A past Chair of the American Association of Pharmaceutical Scientists (AAPS) Process Analytical Technology Focus Group Tim is a member of the Editorial Advisory Board of Pharmaceutical Technology and features on the Industry Expert Panel in European Pharmaceutical Review magazine. Tim is also a committee member of the Particle Technology Special Interest Group at the Institute of Chemical Engineers, Vice-Chair of the D18.24 sub-committee on the Characterisation and Handling of Powders and Bulk Solids at ASTM and a member of the United States Pharmacopeial (USP) General Chapters Physical Analysis Expert Committee (GC-PA EC).
Reprinted in CPHI