 (Paul Tearle/Getty Images)
|
Manufacturers routinely produce stable dosage forms by exploiting the unique properties of powders. Too often, however, powders
display their complex behaviour in uncontrolled ways, potentially compromising process operation and final product quality.
Those working with powders have always amassed experience through successful problem solving and, until recently, more fundamental
knowledge has been scarce. Now, the techniques available for characterizing powder behaviour make it increasingly easy to
combine experience and information, and to correlate process behaviour with a range of powder characteristics. Such correlations,
developed using shear, dynamic and bulk property measurements to rationalize experience, extend our basic understanding, and
make for better powder formulation and improved process design. Here, the example of volumetric dosing allows further experimentation
and exploration of how this can work. Why are powders challenging?
As many as a hundred different parameters can influence powder behaviour. The critical nature of air and moisture content
is widely recognized in the process environment, but many other parameters are also important. Primary factors include particle
size and distribution, shape, porosity, hardness and surface texture. Temperature, vibration, flow rate and storage time are
all good examples of secondary or system variables.
This complexity makes it challenging to define, predict and measure powder properties. Consequently, in contrast to the situation
for gases and liquids, there are few data available for the design, modification or troubleshooting of powder processes. A
fundamental mathematical description of behaviour lies well beyond our current capabilities. Unfortunately, the corollary of this is that powder behaviour is not easily controlled. Maintaining consistent behaviour can
be very difficult when it demands close control of so many variables. For example, in the initial stages of a process, a powder
may have sharp, needle-like particles, but if they are not strong then the size and shape distribution downstream will be
markedly different. Flow properties are likely to be transformed. Alternatively, or indeed additionally, sensitivity to moisture
content may be an issue. Variations in moisture content nearly always affect powder flowability, but the impact is particularly
marked for very hygroscopic materials. A powder that flows freely when relatively dry may become much more cohesive if stored
in damp conditions or processed in a humid environment.
Relevant data are required for optimal formulation, process design and operation, but it is not possible to define powder
properties in terms of the many variables that influence them. The conventional response to this challenge has been to rely
heavily on experiencebased development and operation; an approach that, by its nature, must be relatively inefficient.
Optimizing the value of experience
In general, experience is gathered through trial and error experimentation. For example, with time an operator may learn that
material A processes easily at high rates while material B is more challenging, requiring careful control of specific variables
and a much lower throughput. A third blend may prove almost impossible to process on the same line, but may be easy to handle
in a different piece of equipment. Such experience is not easy to transfer, as it relates only to a specific powder or processing
line. Often, little is known of the underlying reasons for the variability in performance.
Identifying the properties responsible for the excellent performance of powder A and the poor performance of B is the key
to more fundamental process understanding; for example, powder A may perform well because it is freeflowing while B is more
cohesive. If this is the case, then measuring terms that define these aspects of behaviour (e.g., specific energy (SE), basic
flow energy (BFE), shear strength etc.) will facilitate the development of a specification for materials that process well.
Most companies have an extensive experience base, information and observations gathered at the formulation and process development
stages as well as during daytoday operation. Correlating this experience with measured powder properties provides insight
into the practical relevance of specific parameters, optimizing value. Such analysis narrows down the number of variables
that could be influencing process behaviour to the few that actually are. When the factors influencing behaviour, or causing a problem, are understood, steps to change a process or formulation can
be made on the basis of knowledge. Adoption of a knowledge-based approach is the key to Quality by Design (QbD).