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rank the blend's tendency to segregate by sifting. We do not present the complete methodology here, but Table 1 shows the expected relative segregation tendency if sift- ing were the only cause. If we make that assumption, these data suggest that 3.5 percent of the total segrega- tion would be due to the API, 5.3 percent due to MCC, 5.0 percent due to lactose, 72.6 percent due to magne- sium stearate, and 13.7 percent due to glycolate. Angle-of-repose segregation. It is possible to conduct a similar analysis for angle-of-repose segregation because the velocity of particles sliding down the pile is a function of the tangent of the repose angle. If the repose angle is large, then the velocity down the pile is low. If the repose angle is small, then the velocity down the pile is high. Furthermore, the Tablets & Capsules May 2017 23 Table 3 Relative segregation variance for air entrainment Table 5 Quantification of segregation mechanism Table 4 Segregation intensity values for blend Material Normalized angle of repose variance (%) Segregation direction (top or bottom of pile) API 0.3 Bottom MCC 0.0 Top Lactose 0.1 Top Mag stearate 99.4 Bottom Glycolate 0.2 Bottom Material Measured segregation intensity (%) API 16.4 MCC 2.6 Lactose 3.7 Mag stearate 28.5 Glycolate 16.4 Type of segregation Percentage of total Sifting 51.8 Angle of repose 8.2 Air entrainment 40.0 deviation from the average repose angle provides a means of ranking the tendency for angle-of-repose segregation (Figure 7). The complete methodology is not presented here, but Table 2 shows the expected relative segregation tendency if angle-of-repose segregation were the only cause of segrega- tion. If we make that assumption, then 34.6 percent of the total segregation would be due to the API, 2.1 percent due to MCC, 7.2 percent due to lactose, 10.1 percent due to mag- nesium stearate, and 46.0 percent due to glycolate. Air-entrainment segregation. As stated above, air- entrainment segregation depends on both the particles' size and their true density. If the particles are light or small, they are carried further down the pile. Table 3 shows the expected relative segregation tendency when air entrainment is the only cause. If we make that assumption, then 0.3 percent of the total segregation would be due to the API, 0.0 percent due to MCC, 0.1 percent due to lac- tose, 99.4 percent due to magnesium stearate, and 0.2 per- cent due to glycolate. The pattern of the magnesium stearate segregation indicates it accumulates at the top and bottom of the pile. This indicates that the sifting and air- entrainment mechanisms are dominant in this blend. Using the measured segregation intensity (Table 4) and the normalized segregation variance for each mecha- nism, we can determine the percentage of segregation attributed to each segregation mechanism (Table 5). In our example, 51.8 percent of the segregation is due to sifting, 8.2 percent due to angle-of-repose effects, and 40.0 percent due to air entrainment. Process review To illustrate how the process may affect segregation, we will assume that a V-type blender mixes the ingredi- ents into a uniform blend and then discharges it to a tabletting operation below (Figure 9). Note that the transfer occurs in a closed system, with the blender con- nected to a sealed feed hopper. From the hopper, the blend moves through one or more chutes to the tablet press, where it enters the feed frame that fills the dies. Figure 9 Typical tablet press operation Figure 10 Expected segregation in blender after initial charge of feed system Bubbles form during emptying Region high in glycolate