Why is effective powder characterisation so important to the pharmaceutical industry?
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.