Powder Characterization for Formulation and Processing - Pharmaceutical Technology

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Powder Characterization for Formulation and Processing
The current trend within the pharmaceutical industry toward more efficient development, manufacturing, and specification is fueling demand for analytical tools that provide highly relevant information. Effective powder characterization has a valuable role to play.

Pharmaceutical Technology

Optimizing flow-additive concentration

Flow additives such as colloidal fumed silica and magnesium stearate are widely used to improve the flow properties of a blend. An incorrect level of flow additive can be detrimental, with too little producing suboptimal flow and too much promoting lamination of the final tablet. It is understood that lamination, breakage along a plane, occurs when flow additive separates into a layer within the tablet, a process accentuated by high additive levels. Optimizing additive concentration is therefore important.

Figure 2
Figure 2 shows how BFE varies with flow-additive concentration for two different blends that exhibit markedly different behavior. BFE is an extremely sensitive detector of differences in flow behavior and therefore ideal for this type of study. With sample 1, BFE passes through a minimum where there is clearly an optimum concentration. With the second sample, the optimal level may be similar, but it is clear that low additive concentrations have little effect.

Figure 3
Particle morphology can be a dominating factor in terms of how a material responds to a flow additive (see Figure 3). The relatively smooth particles (A to D) will exhibit the behavior shown by sample 1. As flow-additive levels increase, the large particles become more uniformly coated with the smaller lubricating particles, and flow energy decreases steadily. Once all surfaces are coated, excess additive builds in the void spaces, resulting in mechanical interlocking and increased cohesion, hence flow energy begins to increase again.

The irregularly shaped particles (E to G) are initially unaffected by the inclusion of additive because the small particles are unable to provide an effective lubricating effect. Only when sufficient additive has been added to lubricate the contact points between the larger particles is a rapid reduction in flow energy observed (sample 2).

Assessing the likelihood of flooding

Flooding describes the uncontrolled flow of aerated powder, which can be hazardous and is mostly undesirable. Aeration plays an instrumental role in flooding because the air between the particles acts as a lubricant and inhibits the mechanical interlocking that would normally result in a stable bed. Flooding is common with fine but noncohesive materials that easily pick up and retain air.

It is clear that when flooding occurs, little energy is required to make the powder flow. Consequently, measuring flow energy under aerated conditions is effective in highlighting possible problems. Figure 4 shows flow energy as a function of air velocity for two different materials. Measuring the affect of aeration is simple with a powder rheometer because air can be fed at a controlled velocity through the sintered base, up into the powder sample, during testing.

Figure 4
The flow energy of sample A falls markedly with aeration, and that of sample B remains relatively unchanged (see Figure 4). This decrease in flow energy with increasing aeration is symptomatic of noncohesive powders that are prone to flooding and is particularly problematic when combined with a low BFE. Generally speaking, powders with an aerated flow energy ,10 mJ are more likely to fluidize and flood.

Although it is tempting to suggest that flooding is avoided by preventing aeration, this is not a practical proposition because air content cannot be precisely controlled during processing. Powders can easily pick up air, for example during blending or emptying from a keg.


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