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Tablets & Capsules July 2020 15 per with an empty channel in the center above the hop- per discharge. This is undesirable because it leads to inconsistent feeding of material into the tablet press dies and results in tablet weight variation. Due to the poor flow of the Prototype 1 formulation, the scientists selected Prototype 2, which contained 5 per- cent intragranular talc and 1 percent extragranular talc. The dissolution profiles of the prototype batches are shown in Figure 3. As the figure shows, increasing the amount of talc slowed the drug release but only to a minimal extent. Scaling up the reformulated blend After the formulation change, the scientists prepared a second intermediate batch of 40,000 tablets processed using the Gerteis Mini-Pactor. To study the effects of roll force on the granulated blend, they compacted tab- lets at both 10 and 12 kilonewtons roll force with a roll speed of 2 rpm and a gap of 2 millimeters. Table 6 shows the percentage of granules versus fines obtained at each roll force. Altering the formulation to reduce compaction Having determined that the compaction was not the result of the roller compactor type, the scientists intro- duced talc to the scale-up formulation to improve its flow and minimize sticking. The scientists selected talc because literature research revealed that talc can help improve lubrication efficacy. The small particle size of powders means that the material's overall surface area is relatively large, which increases interparticle friction and the development of electrostatic charges, causing cohe- siveness and poor flow. Talc coats the particles, reducing interparticle friction and improving flow. However, the amount of talc used must be optimized to match the level of cohesiveness. According to some studies, talc also increases a roller compactor's mass throughput. This is important because it can allow a high rate of production for scale-up. Additionally, talc reduces the tensile strength of the roller compacted ribbons. The proportion of fines versus granules after roller compaction was shown to play a large role in the proba- bility of compaction occurring. To study the optimal amount of talc to add to the formulation, the scientists manufactured two prototype batches, one with 3 percent intragranular talc and one with 5 percent intragranular talc. They added 1 percent extragranular talc to each pro- totype batch. The compositions of the prototype batches are shown in Table 4. To compensate for the addition of talc, the scientists reduced the percentage of microcrystalline cel- lulose diluent by an equivalent percentage while keeping the percentages of the rest of the ingredients the same. The physical properties of prototype tablets are shown in Table 5 along with the Flodex of the prototype blends. The hardness of Prototype 1 tablets was higher than that of Prototype 2 tablets, while the disintegration of Prototype 2 tablets was slower compared to that of Prototype 1 tablets. However, both prototypes disinte- grated within 25 seconds. The physical properties of the tablets in both proto- type batches were similar, but the Flodex of the Prototype 1 blend was higher compared to that of Prototype 2, indicating poor flowability for Prototype 1. This reduced flowability resulted in weight variation in the Prototype 1 tablets and ratholing of the blend in the tablet press hopper, which is when a cohesive mass of stagnant material forms around the perimeter of the hop- Table 5 Prototype batch physical properties Formulation Hardness (kilopascals) Thickness (millimeters) Friability (percent) Disintegration time (seconds) Flodex (millimeters) Prototype 1 4.73 3.45 0.128 25 14 Prototype 2 4.4 3.9 0.06 14 8 Figure 3 Dissolution profiles of Prototype 1 and 2 tablets 100 80 60 40 20 0 API release (percentage) Time (minutes) 0 15 30 45 60 90 Prototype 1 Prototype 2 Table 6 Percentage of granules versus fines for the refor- mulated intermediate batch (Gerteis Mini-Pactor) Roll force (kilonewtons) Granules (percentage) Fines (percentage) 10 63.2 36.8 12 64.3 35.7