Why is effective powder characterisation so important to the pharmaceutical industry?
Tim Freeman
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Understanding and controlling powder behaviour can help to formulate clinically effective products, design efficient processes
and, ultimately, manufacture a consistently high-quality product; this is particularly important in the pharmaceutical industry
where the majority of APIs are delivered as powders — for inhalation, dissolution for intravenous use, or for ingestion as
tablets or capsules. Effective powder characterisation has long been recognised by the pharma industry as providing core knowledge
that informs powder understanding and control, and many powder measurement methods have been devised in response.
In today's industry, Quality by Design (QbD) and economic pressures have increased the emphasis on manufacturing efficiency
and product quality. QbD suggests 'ground up' development of robust manufacturing processes that consistently deliver in-specification
product without excessive reliance on QC, while economic pressures, arising from low yields, lengthy time to market and an
active generics market, make it vital to ensure optimised production from the outset. Because the seeds of successful manufacture
are sown during the earliest stages of a project, it is important to employ a more holistic approach to product and process
development. Tools that deliver relevant, reproducible powder property data provide a common language and can help break down
the traditional barriers between formulators, process designers and manufacturers.
Powder characterisation is also growing in importance because innovation in the industry is increasingly reliant on sophisticated
technologies, which intensify powder handling challenges. Highly potent actives, incorporated in extremely small proportions
pose one set of issues; newer delivery technologies, such as dry powder inhalers (DPIs), another. DPIs are a practical way
of delivering systemic drugs, especially where molecules are too delicate to survive the gastrointestinal tract, but the powder
engineering involved is demanding.
Why are powders difficult to characterise?
The extensive range of powder testing methods used in the pharmaceutical industry (and elsewhere) highlights both the importance
and the difficulties of powder characterisation. Many simple techniques (angle of repose, flow through an orifice, Carr's
Index) have some intuitive logic and provide insight, but reproducibility and process relevance are common problems. Understanding
why is crucial for both measurement and processing success.
Many variables influence powder behaviour. Primary factors include particle size, shape, surface energy and roughness, but
secondary or system variables will also have a profound impact; for example, the degree of aeration and the level of moisture.
In many industrial systems, the only known variables may be particle size, particle shape and composition, with other relevant
parameters remaining unquantified. Furthermore, the science of powders is not sufficiently advanced to predict performance
from all contributing factors, making a mathematical approach to powder characterisation impractical for most industrial applications.
This indicates that reproducible measurement and, for analogous reasons, consistent processing, depends on keeping a significant
number of influential variables constant. A sample extracted from a high-shear mixer and analysed immediately could exhibit
flow properties that are very different from an otherwise identical sample given time to release air and consolidate under
its own weight. Addressing this issue is essential for reproducible testing. High reproducibility is, in turn, the key to
sensitive differentiation between different powders. 'Noisy' data makes it much harder to distinguish between a sample anomaly
and an analytical artefact.
Certain modern powder testers improve reproducibility by conditioning the powder ahead of measurement, minimising the impact
of packing history. Gentle agitation before analysis releases excess air or dissipates consolidation, leaving a homogeneous,
loosely packed bed for baseline measurement. Adding automation ensures a welldefined analytical procedure and removes other
potential sources of variability, such as the operator! Together, these strategies take the reproducibility of newer instruments
far beyond levels achieved with many traditional tests, and, more importantly, modern powder testers add new test methodologies
and techniques that extend our powder knowledge.
For instance, a test such as angle of repose is attractive because of its simplicity, but provides only a single number description
of a powder, which is inadequate for modern needs. Measuring an array of powder properties is essential because powders have
many characteristics. The parameters that best describe behaviour in a tabletting compression process, for example, are not
those that most precisely reflect aerosolisation performance in a DPI, or during mixing. Consequently, instruments that incorporate
a range of measurement techniques offer advantages. For manufacturing-related studies, the inclusion of dynamic test methods
is especially beneficial.
