Assessing powder stability

By Reg Freeman, Freeman Technology Some powders appear inherently variable, sensitive to the slightest change in conditions, while others are much more forgiving. Stability testing assesses this critical aspect of powder behavior. Powders sometimes behave in unpredictable ways a once free-flowing powder sets solid, or a homogeneous feed delivers a product of inconsistent composition. The material appears to have changed, with severe implications for operation, but the underlying causes are far from obvious. The changes may be reversible, but in some cases are not, in which case original performance is unlikely to be regained. Such variability is unique to powders - other materials exhibit much greater consistency and predictability. Why powders are different Powder properties, like those of any material, are a function of certain variables. Controlling these controls behavior. For gases and liquids, setting temperature, pressure and composition defines material properties, but with powders the situation is much more complex. Powder behavior is influenced by a whole array of variables. Some are features of the particles themselves - size, shape, surface roughness, hardness, porosity, for instance - while others are connected with the system as a whole; air content, humidity and vibration being prime examples. This complexity makes it very difficult to maintain consistent powder properties, since potentially it demands the control of many parameters. Some powders are inherently variable. Others are less markedly affected by fewer variables and are much more robust. Stability testing quantifies this vulnerability to change. The causes of instability Consider a press that periodically produces tablets with inconsistent distribution of the active pharmaceutical ingredient. Detailed investigation reveals that there is a problem with segregation of the feed under certain conditions. Segregation is the separation of particles of unequal size and can be an issue for pharmaceutical blends since the active pharmaceutical ingredient is often very fine. It is a physical process that can be reversed by mixing the material until it is homogeneous once more. Here then variability or instability is induced by segregation and is therefore reversible. Attrition on the other hand is an irreversible cause of variable behavior. If particles are broken down during processing fines will be generated, any surface coating removed and of course particle size and distribution will be altered, resulting in a significant change in flow properties. The solution may be to avoid aggressive handling operations such as pneumatic conveying, or alternatively improve the flow properties of the brokendown powder, perhaps through the use of additives. Returning the particles to their original form, however, is not likely to be an option. The response of the processor to instability in a material will be influenced by whether or not it is reversible, so it can be useful to classify on this basis. Some causes, however, fall into an intermediate third category, since whether the change they induce is reversible or not depends on the material. Table 1 provides some examples of the factors responsible for instability. Table 1 Examples of the causes of instability Causes of instability that are usually reversible Segregation Compaction Vibration (particle interlocking) Aeration Causes of instability that are usually irreversible Attrition Caking Coating loss Chemical reaction Causes of instability that may be reversible Agglomeration Moisture Electrostatic charging

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The impact of instability Instability in a powder influences testing, processing, and specification. One of the reasons why so many powder characterization techniques produce variable results is that they dont ensure that the powder is measured in a consistent state. With powder rheometers the concept of conditioning the powder prior to measurement has been introduced to greatly improve reproducibility. Gently disturbing the powder bed in a closely controlled way eliminates the impact of processing history. Weak agglomerates are dispersed and excess entrained air is released to produce a homogeneous loosely packed bed that provides a consistent baseline for measurement. Reproducible, accurate analysis promotes better specification setting. If the measurement technique is inaccurate then differences between samples cannot be reliably identified as being real. Correlating accurately-measured powder properties with performance makes it possible to closely define product quality criteria, but with an unstable powder this will always be quite challenging. In terms of processing, instability usually makes for more difficult control as even slight changes can cause a dramatic shift in behavior. Stopping the process for only a brief time, for example, may result in de-aeration of the powder and blocking of the lines, or operator-to-operator variations in silo filling method may impact segregation. It is clear then that identifying instability in a powder, and its causes, is important, so, how is this done? Assessing stability Reversible and irreversible instability can be detected using a powder rheometer, an instrument that allows dynamic characterization of a sample i.e. measurement of a powder in motion. The force and torque acting on a blade as it rotates through the material is measured, to quantify the energy needed to induce and maintain flow under different conditions. A key dynamic measure is Basic Flow Energy (BFE). To determine BFE the blade is rotated down through the sample, compacting the powder against the base of the sample vessel. Conditioning prior to measurement eliminates the effects of inherent powder variability so analysis is both reproducible and repeatable. As a result BFE is a highly differentiating parameter. Repeating the BFE measurement cycle (condition and test) a number of times, typically around seven, detects instability. If BFE remains constant then the powder is stable. If, on the other hand, it either decreases or increases then testing or processing is changing the material. A powder exhibiting this characteristic is inherently unstable. Analyzing stability data

Figure 1 Examples of stability test data Examples of stability test data are shown in figure 1. The first sample is stable, BFE being essentially constant in successive measurements. The other two samples exhibit different types of instability; with one BFE increases as testing proceeds, with the other it decreases.

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Stability can be quantified using a stability index (SI), defined as the ratio of the BFE value in the final test to that in the initial one (see above). The sample with an increasing BFE will have a stability index in excess of one, while that for the other unstable sample will be less than one. Any value outside the range 0.9 1.1 is an indication of instability; the greater the number the more marked the observed effect. So, the stability test data is generated and the sample is stable. This makes subsequent testing relatively easy, as the test process itself is not having an impact on measured results. The powder can be characterized as required. More importantly processing is also potentially easier although powder behavior may still be radically affected by variables such as air content, degree of humidity etc. But what if the results show the sample is unstable? Materials with a stability index greater than one become more resistant to flow as they are processed while those with an index of less than one flow more easily in successive tests. There are multiple causes of both types of behavior so it is often necessary to consider other powder properties when rationalizing the reasons for instability. It is also important to realize that two or more factors may simultaneously influence stability, perhaps even off-setting each other. For example, attrition of the initial particles may produce fines, promoting segregation; two causes of instability, one irreversible and one reversible. Factors commonly responsible for a stability index greater than one: De-aeration Some powders, particularly those that are cohesive, retain air, as the particles tend to pack relatively inefficiently. Testing squeezes this air out making the sample progressively denser or stiffer and more resistant to flow. BFE therefore increases with processing/testing. Agglomeration Another feature of cohesive powders is their propensity to agglomerate. As the primary particles move relative to one another cohesive forces bind them together, forming agglomerates. As with de-aeration this increases density, and flow energy rises correspondingly. Segregation Many powders have a broad size distribution or contain distinct populations of differently sized particles. This may simply be a consequence of the manufacturing process or intentional, as fine particles are often used as flow additives. When segregation occurs, smaller particles usually sink to the bottom of a container while larger particles rise to the top. This process reduces any lubricating effect the fines may be having, usually producing an increase in flow energy. The opposite can also occur however, if the separated populations have better flow properties than the combined sample. Segregation is promoted by agitation of the powder or simply causing it to flow. Moisture uptake Powders that are hygroscopic may absorb water during testing. The particle may swell, as a result, or there may be an increase in surface frictional forces, if water adheres to the particles. In either case flow energy will increase. Electrostatic charging Some powders easily collect electrostatic charge, often because of their chemical composition or the very low moisture content of the system. Tribocharging is the most commonly encountered problem where particles develop a charge as they rub together. If this charge doesnt dissipate it will increase the forces of attraction between particles, reducing the ease with which they flow.

Factors commonly responsible for a stability index of less than one:

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 Attrition Mechanical stresses applied during processing can fracture particles especially if they are brittle and friable. Attrition causes wear mainly the removal of corners so that fines are produced and a somewhat smaller and rounder particle remains. Such particles tend to flow more easily so testing would exhibit a reducing SI, providing the level of fines present is not excessive. Fractured particles, on the other hand, generally increase resistance to flow so that testing produces an increasing SI, as particles break up. Mechanical stresses can therefore induce varying results depending on particle and powder characteristics. De-agglomeration De-agglomeration produces a similar effect to attrition although in this case it is agglomerates rather than primary particles that are being broken down. Improved blending of a flow additive One of the factors influencing the effectiveness of a flow additive is its distribution within the sample. To reduce particle-particle friction throughout the powder bulk it must be evenly dispersed. If it isnt initially, then stability testing will essentially continue the blending process. As testing proceeds the sample will become progressively more homogeneous, promoting the activity of the flow additive. Flow energy will consequently fall. Coating of the test blade and vessel As well as being used to promote flowability, flow additives are used to reduce the friction coefficient between a formulation and processing equipment, particularly in tabletting applications. Additives such as fumed silica and magnesium stearate perform this function extremely well, but as a result have a tendency to contaminate any surface they come into contact with. These materials easily coat the blade of a rheometer and the sample vessel causing a progressive reduction in flow energy as testing progresses. While this may compromise stability assessment it can be a useful effect. Testing with different levels of additive makes it straightforward to identify the concentration required to minimize friction between the test equipment and the sample. This helps with optimization of flow additive concentration. Interpreting less commonly encountered stability data In the above examples flow energy is consistent or rises and falls to a steady level during a seven-stage test cycle. Figure 2 shows two different sets of data.

Figure 2 Examples of unusual stability test data The data on the left indicate a powder with some level of stability as there is no upward or downward trend in flow energy, however the values measured fluctuate quite dramatically. This behavior is most commonly observed with very sticky or cohesive materials. These powders are so prone to forming agglomerates that the process of conditioning is enough to promote cohesion. The erratic nature of the measurements is symptomatic of the continuous formation and breakdown of agglomerates in subsequent tests.

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In the other set of data (figure 2) flow energy has not reached a stable value and is still falling. If a stable value is not reached during routine testing then the test cycle should be extended. Stability testing should ideally continue until three tests have produced similar results, two if the profile is very smooth. A stable sample is required for further characterization because if flow energy is constantly changing it is impossible to assess the impact of any other variable. In conclusion Some powders appear to be fundamentally less stable than others, erratic during processing and unpredictable. These powders can be challenging and indeed are best avoided if possible. Stability testing highlights this fundamental aspect of powder behavior and processability and is therefore a valuable tool at the development stage or when troubleshooting. It is also an intrinsic and important part of accurate powder characterization, as other properties cannot be measured with any confidence without establishing a steady baseline for comparison. Assessing powder stability, the causes of any instability and whether changes are reversible or permanent, is therefore essential for effective product development and processing. However, since changes can be either temporary or permanent, and more than one cause of instability can be in evidence at any given time, the subject is challenging.

June 2008 Reg Freeman Tel: + 44 (0) 1684 310860 www.freemantech.co.uk reg@freemantech.co.uk

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