Multivariate Approaches for Powder Characterization

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Dynamic testing and advances in shear testing provide better insight into powder physical properties and external variables that affect powder behavior.

Although traditional powder-characterization methods, such as Carr’s Index, the Hausner Ratio, flow through an orifice, and the angle of repose, provide some information, these techniques may have limited value given the processing technologies in use today in the pharmaceutical industry. John Yin, an applications specialist with Freeman Technology, spoke with Cynthia Challener, editor of the Pharmaceutical Sciences, Manufacturing & Marketplace Report, about the importance of newer powder-characterization techniques for optimizing pharmaceutical product development and manufacturing processes.

Powder properties affect processing behaviorPharmaceutical Sciences, Manufacturing and Marketplace Report: Why is powder characterization so important for the pharmaceutical industry? When is it used and what impacts does it or can it have?

Yin (Freeman): Understanding and characterizing powder behavior is critical for the production of solid-dosage formulations, and there are many key properties of powders that determine how they will behave in a hopper, when being filled into a die, and compressed into a tablet. Understanding the variables and processing conditions involved in relation to what powders are required to do is therefore relevant during all aspects of development and manufacturing, and can provide information that can be used for formulation development, process optimization, and improvement of the quality of the final drug product.

Value in a multivariate approachPharmaceutical Sciences, Manufacturing and Marketplace Report: What advances in powder characterization have been achieved in recent years? What drove these developments; what unmet needs were addressed?

Yin (Freeman): In the past, much of the focus on powder characterization has been at the single aspect level where one standard or number is expected to dictate ‘good’ or ‘bad’ once and for all. In reality, we rely on multiple techniques for explaining behavioral differences when being subjected to many processing conditions. While some information can be obtained with traditional methods, such as bulk-tapped density, flow through an orifice, and angle of repose, these techniques are not at all representative of the conditions that powders see under process conditions and, therefore, are not able to provide process-relevant and differentiating information given the process technologies in use today in the pharmaceutical industry.


The multivariate approach for characterizing powders has made it possible to gain much greater insights into how the combination of powder physical properties and external variables affect their behavior. Dynamic testing for example, which measures the flow energy of a powder with respect to external conditions, such as aeration, flow rate, and consolidation, is a newer technique enjoying considerable industrial uptake. Advances in shear testing are also improving both the precision and reproducibility of this important analytical method.

More meaningful data equals more controlPharmaceutical Sciences, Manufacturing and Marketplace Report: What specifically does Freeman's new system bring to the pharma industry?  What were the reasons for its development? How is it differentiated from other systems on the market?

Yin (Freeman): The FT4 Powder Rheometer can conduct seven direct measurements that fall into the three major categories of bulk, dynamic, and shear powder properties. In addition, we have developed software that incorporates state-of-the-art mathematical modeling of powder properties in order to help customers use the data to predict the compatibility between a powder and manufacturing equipment (i.e., a hopper).

In the bulk-property category, we can determine bulk density, compressibility, and air permeability, all of which affect the ability of the powder to undergo tableting processes. Shear properties are measured to predict how the powder will behave in a hopper. Dynamic flow properties are designed using special blade methodology that measures flow energy as a function of aeration, flow rate, and consolidation.

Importantly, the system is designed to condition a powder first before making any measurements. Conditioning involves the generation of a standardized packing condition through gentle displacement of the entire powder sample in order to loosen and slightly aerate it. The result is a homogenously packed powder bed with no precompaction or excess air.

The system is automated and has been demonstrated to reproducibly deliver reliable data that correlate with process performance. Because we are able to measure a meaningful and relevant set of powder properties, this information can then be used to numerically describe, rationalize, and better understand core powder-processing operations. It has, for example, been used at line to very rapidly correlate the impact of the moisture content in a powder to the properties of a final, formulated product and to characterize powders and their behavior in order to quickly optimize continuous granulation and tableting processes.

Steep learning curvePharmaceutical Sciences, Manufacturing and Marketplace Report: What limitations remain with respect to powder-characterization technology for the pharma industry? Why are these issues important?

Yin (Freeman): One of the biggest limitations at this point is the lack of understanding of powder behavior at the level needed to describe such behavior mathematically or from an axiom perspective. There are so many variables, not just particle size and density, which are often perceived as the only critical factors that influence powder behavior, but also the surface texture, particle shape, stiffness, and porosity as well as external influences, such as air, moisture, consolidation stress, and flow rate, which can all contribute to the picture. There is much work to be done in this area and it will be a steep learning curve. A second challenge is the need to make the pharmaceutical industry and other powder-processing industries (that share similar challenges) aware of the benefits of more comprehensive powder characterization. We are working on addressing both issues.

Climbing the curvePharmaceutical Sciences, Manufacturing and Marketplace Report: What advances in powder-characterization technology might be expected? What specifically is Freeman working on?

Yin (Freeman): The adoption of continuous manufacturing for the production of solid dosage forms will have an impact on powder-characterization technology. In addition, as the amount of data gathered on different powder systems increases, we will continue to gain more knowledge about powder properties and behavior and be able to expand our insight into performance with respect to different processing conditions.

At Freeman, we always seek room for improvement based on the feedback that we get from current users. We are learning a great deal and using that new knowledge and experience to improve both our software and instrument design. At this time, however, it is not possible to provide any specifics.