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22 May 2017 Tablets & Capsules Particle size of components in blend and driving force for air entrainment Cumulative distribution (%) Particle size (micron) 0.1 1 10 100 1000 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Blend Lactose Mag stearate Glycolate Ideal MCC API Accumulation at top Accumulation at bottom Material True density (kg/m 3 ) API 1120 1570 1540 1090 1490 MCC Lactose Mag stearate Glycolate Particle size of components in mixture and driving force for sifting Cumulative distribution Particle size (micron) 0.1 1 10 100 1000 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Blend Lactose Mag stearate Glycolate Ideal MCC API Accumulation at top Accumulation at bottom Repose angles of components in blend Percentage of total Repose angle (deg) 10 20 30 40 50 60 70 80 40% 30% 20% 10% 0% Blend = 10.0% Lactose Mag stearate Glycolate MCC API Accumulation at top of pile Accumulation at bottom of pile tration of one increases, it induces a decrease in the other's concentration, and this occurs in almost equal amounts. Because of this symbiotic relationship, the blend's total concentration of bulking agents is less prone to segregate. Note how conducting these two simple segregation tests—fluidization and pile formation—provides sufficient information to get a very good idea of where different ingredients might end up in a typical tablet press feed sys- tem. The root cause(s) of the segregation, however, are not yet fully quantified. That requires additional information. Other segregation mechanisms Next, let's see what happens when the blend is sub- jected to each unique segregation mechanism. In sifting segregation, fines pass through a matrix of coarse particles. This type of segregation is driven by differences in particle size and the degree to which the voids between particles are filled with particles of sufficient size to prevent the pas- sage of small particles (Figure 5a). When segregation arises due to a difference in repose angle, it is because ingredients with different frictional surfaces slide at different velocities down a pile (Figure 5b). Just 2 degrees of difference in this angle can cause significant segregation. The other segrega- tion mechanism we will investigate is caused by fines being carried by air currents during the filling process (Figure 5c). In this scenario—air-entrainment segregation—parti- cle size and the true density of the particles are the drivers. Sifting segregation. In the ideal particle size distribu- tion—which can exist—all voids are filled with particles of the appropriate size (Figure 6). The difference in cumulative concentration between the ideal particle size curve and the blend's particle size curve enables us to Relative segregation variance for sifting Material Normalized sifting segregation variance (%) Segregation direction (top or bottom of pile) API 3.5 Top MCC 5.3 Bottom Lactose 5.0 Bottom Mag stearate 72.6 Top Glycolate 13.7 Top Relative segregation variance for angle of repose Material Normalized angle of repose variance (%) Segregation direction (top or bottom of pile) API 34.6 Top MCC 2.1 Bottom Lactose 7.2 Bottom Mag stearate 10.1 Top Glycolate 46.0 Bottom Figure 6 Figure 7 Figure 8 Table 1 Table 2