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14 July 2020 Tablets & Capsules method as for the proof-of-concept batch. However, because the Freund-Vector TFC roll compactor is a lab- scale machine designed for a throughput of 5 grams to 1 kilogram per hour, they used a Gerteis Mini-Pactor for the granulation step. The Mini-Pactor is capable of handling batches as small as 10 grams up to small-scale production batches, with a maximum output of 100 kilograms per hour. Also, the TFC is a fixed-gap roll compactor, so if the amount of powder drawn into the compaction area is inconsistent, the force applied to the powder bed will vary. This can cause variability in the ribbon and granule properties. The Mini-Pactor, on the other hand, is a floating-gap type roll compactor, wherein the distance between the rolls changes depending on the amount of powder fed so that the force applied to the powder remains constant. This leads to a more consistent compaction process and less variability in the ribbon and granule properties. In addition, the Mini-Pactor has an in-line oscillating mill, which is gentler on the granules compared to the off-line Comil or Fitzmill that is used with the TFC. The blend was roller compacted at 8 kilonewtons roll force and a 2-millimeter gap. The roller compacted rib- bons were milled using a star rotor equipped with a 0.8-millimeter screen. The fines were recirculated to obtain a concentration of less than 15 percent, which was consistent with the process used to granulate the proof- of-concept batch. Table 3 shows the resulting percent- ages of fines and granules. The percentage of fines decreased as the fines were recirculated back to the roller compaction process. The scientists compressed the tablets for the interme- diate scale-up batch using a rotary tablet press equipped with a force feeder. They observed that the blend was severely compacted in the feeder and that the feeder compacts could be easily broken on contact. This indi- cated that the blend was somewhat cohesive and prone to agglomeration in the feeder. To determine if the energy imparted by the feeder paddles was exacerbating the blend's cohesiveness, the scientists compressed additional tablets on a rotary tablet press equipped with a gravity feeder with no paddles and observed a similar blend compaction. The scientists then hypothesized that the blend's high cohesive energy could be resulting in compaction of the blend in the feeder. To study the issue, the scientists manufactured a larger batch using the TFC roll compactor to see if blend com- paction was an effect of the larger batch size, or whether it might be related to feeding-mechanism differences between the two different roll compactors. With the TFC roller compactor, the same blend com- paction occurred at the neck of the hopper after 15 min- utes of run time that had occurred with the Mini-Pactor. The scientists observed the blend adhering to the rollers and the neck of the hopper, as shown in Figure 2. This indicated that blend compaction was a result of the larger batch size and not of the equipment. Table 3 Granules versus fines for intermediate scale-up batch after roller compaction Granules (percent) Fines (percent) First pass 55 45 Second pass 78.6 21.4 Third pass 91.6 8.4 Table 4 Formulation composition of prototype batches Ingredient Percentage Prototype 1 Prototype 2 Intragranular Compound X 35.00 35.00 Microcrystalline cellulose 54.50 52.50 Croscarmellose sodium 2.50 2.50 Talc 3.00 5.00 Magnesium stearate 0.50 0.50 Extragranular Croscarmellose sodium 2.50 2.50 Talc 1.00 1.00 Magnesium stearate 1.00 1.00 Figure 2 Formulation adhering to roller compactor rollers (a, b) and hopper neck (c, d) a. b. c. d.