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Quantifying experience in powder processing: enshrined in the concept of quality by design is the premise that optimized pharmaceutical manufacturing requires detailed understanding of products and processes. With this in mind, many benefits can be achieved by combining modern powder characterization techniques with real processing experience.

Article Excerpt
Manufactures 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 experience-based 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...