PharmTech: In your experience, What attributes besides particle-size distribution must be considered for tableting processes?
Freeman (Freeman Tecnology): As the industry focuses on better manufacturing efficiency, there is greater interest in identifying powder properties that
directly influence tableting in-process performance and final product quality. Particle-size distribution is a critical primary
particle characteristic of powders, but it is only one of many variables that impact bulk powder properties, which in turn
dictate in-process behavior and product quality. Bulk property measurements can be an efficient way of accelerating and supporting
process optimization studies because they quantify the net effect of all primary particle properties (e.g., size, shape, texture,
surface energy and porosity), whether these can be measured directly or not. Furthermore, even if all primary particle properties
that influence in-process behavior could be measured, the mathematical relationship between bulk powder behavior and particle
characteristics remains elusive and highly complex. Hence, the most effective way forward is to measure process relevant characteristics
of the bulk powder.
WALTER B. MCKENZIE/PHOTODISC/GETTY IMAGES; COMPOSITING BY DAN WARD
Tablet production can be divided into at least four discrete processes: discharge from the hopper; flow into and through the
feedframe; die filling; and compression. Each of these processes subjects the powder to a specific set of environmental conditions
(e.g., flow rates, stresses, and equipment surface properties), making different bulk properties more relevant at different
stages. I would highlight the following as especially valuable:
Dynamic flow properties (including Basic Flowability Energy, Specific Energy, Aerated Energy, and Flow Rate Index): to optimise
the flow regime in the feedframe and the efficiency of die filling, to investigate the effect of paddle geometry, to assess
the likelihood of attrition, segregation and agglomeration.
Shear properties: for optimising flow from the feed hopper, where shear properties of powder–powder and powder–wall are important.
Permeability and compressibility: for assessing how easily the powder can transmit air and the impact of compression on the
powder. Both characteristics are important during the filling and compression steps.
Levoguer (Malvern Instruments): Success in tableting does indeed depend on many factors. It is important, for example, to control the flowability and compressibility
of the tableting blend, as well as any tendency towards segregation, to ensure the production of uniform tablets at the required
rate. Particle size and particlesize distribution are recognised as critical material attributes because they are known to
directly impact these properties, as well as others such as solubility and bioavailability, which may define clinical efficacy
as highlighted in ICH Q6A.
As analytical techniques evolve, however, it is becoming easier to identify other parameters that also impact behavior in
the tablet press. Here I would highlight particle shape, a parameter that, like particle size, is known to affect powder flowability
and segregation. In the past, shape information was gathered by microscopy, but the advent of automated imaging has made it
much faster and easier to access statistically relevant data. Such information forms a foundation for scientific investigation
of the impact of shape and supports the development of more successful tableting blends.