Roller Compaction of Anhydrous Lactose and Blends of Anydrous Lactose with MCC - Pharmaceutical Technology

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Roller Compaction of Anhydrous Lactose and Blends of Anydrous Lactose with MCC
The authors studied the behavior of anhydrous lactose and the combination of anhydrous lactose and the combination of anhydrous lactose with microcrystalline cellulose on a pilot-scale roller compactor.

Pharmaceutical Technology

Results and discussion

Figure 3: Ribbon temperature versus roll pressure. MCC is microcrystalline cellulose; MgSt is magnesium stearate.
Roller compaction. Three placebo blends were roller compacted: 99.25% SuperTab 21AN with 0.75% magnesium stearate; 65% SuperTab 21AN with 35% Pharmacel 102; and 55% SuperTab 21AN with 45% Pharmacel 102. The ribbons did not stick to the roll surface throughout the 20-kg runs. When anhydrous lactose was used as the sole excipient, it was necessary to add some lubricant to prevent the ribbon from sticking to the rolls. The addition of 0.75% magnesium stearate was sufficient. Roller compaction of blends consisting of anhydrous lactose with 35% or 45% MCC required no lubricant to prevent sticking on the knurled roll surface.

Figure 4: Particle-size distribution of the SuperTab 21AN 65%, microcrystalline cellulose 35% blend after roller compaction at different pressures and after milling.
The temperature of the ribbons was measured during roller compaction. Rolls were cooled with flowing water at a temperature of 14.6 °C. The temperature of the ribbons rose as the process started but stabilized within 5 min for all three blends. Figure 3 shows the stabilized temperature for the three blends at the five roll pressures. The temperature increased with increasing pressure and was slightly higher for blends containing MCC. Increases in temperature are primarily caused by the densification process of the powder but also by work exerted by the vertical precompression screw. The MCC flows less well than SuperTab 21AN and deforms plastically upon compaction compared with the brittle fracture of SuperTab 21AN. These two differences could be the cause of the temperature elevation.

Table I: d50 data of the granules.
A further assessment of the powder blends was made by measuring the throughput. Upon addition of MCC, throughput decreased from 46.0 (0% MCC) to 39.4 (35% MCC) and 41.0 kg/h (45% MCC), which is a reduction of as much as 14%. This decrease was a result of the lower bulk density of the MCC, which shows that at a given roll speed, throughput can be increased by increasing the anhydrous lactose content in the formulation.

Figure 5: Particle-size distribution (PSD) of the three placebo blends at a roller compactor pressure of 6.3 kN/cm.
Granule testing. Ribbons formed by roller compaction were milled into granules. For the purpose of this study, mill settings were kept constant for all formulations and roll pressures. Particle-size analysis showed that as roll pressure was increased, the particle size decreased (see Table I and Figure 4). As the ribbons hardened, the milling intensity of the precompacted material increased, resulting in the production of more fines. Optimizing the mill speed and screen size opening may prevent this effect, but this option was not researched further during this project.

Figure 6: Poured bulk and tapped densities of the granules and powder blends (0 kN/cm is the powder blend; AL is anhydrous lactose).
Only small differences were observed among the blends. Figure 5 shows that the particle-size distributions of the various blends are similar after compaction and milling under the same circumstances. Figure 6 shows the resulting poured and tapped bulk densities of the granules made from three different blends. Both poured and tapped densities decreased as MCC was added to the blend. As roller pressures increased, the bulk density of the anhydrous lactose granules decreased slightly. and the tapped density remained constant.


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