Segregation Sifting

The primary mechanisms responsible for most particle segregation problems are sifting, particle velocity, air entrainment, particle entrainment, and dynamic effects (14). 

Another technique is to change the particle size distribution. There are, however, disadvantages. If segregation is occurring by the sifting mechanism, the particles must be almost identical in size before sifting is prevented. Alternatively, the mean particle size can be reduced below 100 p.m, but this size reduction (qv) increases the probabiUty of segregation by the too fine powder mechanisms. 

Relative motion can be induced, for example, as a pile is being formed, as particles tumble and slide down a chute. The result of sifting/percolation segregation is usually a side-to-side variation of particles. In the case of a bin, the smaller particles will generally be concentrated under the fill point, with the coarse particles concentrated at the outside of the pile (Fig. 4). 

Figure 4 Photo of sifting segregation after pile formation light-colored fines remain in the center, while darker, coarse particles concentrate at the perimeter.

Standard Practice for Measuring Sifting Segregation Tendencies of Bulk Solids. ASTM Standard D6940-03. ASTM International, 2003. 

Reduce the mobility of the API, by mechanically binding the API to the formulation excipients Quality Granulation fluidization and sifting segregation potential Tablet content uniformity... 

A fifth process challenge in the optimization of a dry granulation process is to achieve a granulation that is resistant to fluidization and sifting segregation forces. In general, process parameters that influence segregation potential are similar to those that influence variability in sieve cut potency. 

Therefore, for a given formulation (brittle vs ductile), a balance in the level of applied compaction force and roller gap width must be identified to control factors that influence tablet content uniformity (variability in sieve cut potency, sifting, and fluidization segregation) without sacrificing factors that influence manufacturability (compression force required to achieve target tablet hardness). 

ASTM D 6940-03. 2003. Standard practice for measuring sifting segregation tendencies of bulk solids. In Annual book of ASTM standards, vol. 04.08. 

Besides theoretical prediction tools,63 commonly used devices include fluidization segregation testers and sifting segregation testers. The Jenike and Johanson fluidization tester is standardized through ASTM International.64 The tester fluidizes a powder sample (80 mL) in a column of air and allows the particles to settle in the column. The tester has a mechanism to retrieve top, middle, and bottom samples of the settled powder. The sample is then analyzed to determine if there is a property gradient within the column. However, the tester can be improved by making it material-sparing, more efficient, and more reproducible. 

In direct-compression formulation, there is a wide particle size distribution. Usually, the active drug is at the fine end of the range. Such a wide particle size range can easily result in significant segregation. Five primary mechanisms are responsible for most particle segregation problems [13]. Of these, only three typically occur with pharmaceutical powders sifting, entrainment of air, and entrainment of particles in an air stream. 

FIGURE 8 Example of sifting segregation in a (wo-dimcnsional pile. Note the dark particles arc approximately 1200 pm. while the light particles are approximately 350 pm. Source Courtesy of Jenike Johanson, Inc. 

It uses a smaller test sample, and provides unit-dose samples for analysis. An alternate way to run the sifting segregation test involves cycling the blend multiple times to strengthen the segregation " signaP" (59). 

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