Continuous Improvement in Tablet Coating and Dry Granulation - Pharmaceutical Technology

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Continuous Improvement in Tablet Coating and Dry Granulation
Recent advances in equipment design and operation in spraying, drying, and mixing can improve the tablet-coating process.

Pharmaceutical Technology
pp. s12-s16

Roller-compactor case study

The aim of the following study is to show and prove the functionality of this type of sophisticated dry granulator.

Materials and methods. A powder mixture (1:1 ratio) consisting of lactose and microcrystalline cellulose was used for roller compaction. For lubrication, 0.5 % magnesium stearate was added. The excipients were premixed in a bin blender. The homogeneous blend was roller-compacted at different compaction forces and different sieve setups. A smooth master roll and a grooved slave roll of 100-mm width were used for the compaction trials. Sampling was performed after the process start-up when steady state was reached. Final granules were manually subsampled and analyzed in duplicate by mechanical sieving.

Compaction force. The impact of the compaction force on the final granule particle size was analyzed at 2-rpm roller speed, 300 rpm for the 1.5-mm rasp sieve, and a gap width of 2.5 mm. The process began with an activated PID loop control for the feeding system. Steady state was achieved within 40 seconds with a constant specific compaction force and a constant gap width. Thus, a minimal material loss could be detected due to the quick loop control.

During processing, the compaction force was increased step-wise, so that the next force level was quickly achieved within seconds. Deviations of the specific compaction force were below 0.1 kN/cm and 0.1 mm for the gap, respectively. Thus, both parameters could be considered constant during processing.

Granule particle size increased with higher compaction force levels. After granulation, through a 1.5-mm rasp sieve, the amount of fines (particle size < 100 m) ranged from 39% for the granules compacted at 5 kN/cm to 11% for granules prepared at a 15-kN/cm compaction force. Compaction at such a high force level led to a higher amount of coarse granules (> 2000 m). Therefore, a smaller screen size between 1 mm and 1.5 mm is recommended to minimize this large granule fraction.

Gap width. Material throughput during roller compaction can be increased with a larger gap width. It was reported in the literature that a larger gap width at a constant compaction-force level leads to finer granules (4). This effect could not be observed when compacting the powder mixture at 10 kN/cm.

At 2-rpm roller speed and 300-rpm sieve speed (1.5-mm rasp sieve), comparable granule particle-size distributions were obtained although the gap width was increased from 1.5 mm up to 3.5 mm. A homogeneous application of the compaction force over the whole roller width could be one reason for the similar granule size. Thus, material throughput could be easily increased without a change in granule properties.

Sieve setup. The applied compaction force mainly affects granule particle size. Secondly, the setup of an integrated granulation unit determines the final particle-size distribution. With increasing screen size, coarser granules are obtained.

The rasp sieves with 1.5-mm and 2-mm screen size led to similar granule particle-size distributions at 300-rpm sieve speed. In comparison, the 1-mm rasp sieve led to finer granules with higher amount of fines. Finally, all three screen types led to acceptable amounts of fines due to the gentle cutting behavior of the rasp sieve during granulation. The choice of the right screen size makes it possible to influence the final granule particle size distribution.

A further possibility to vary the sieve setup is the alteration of the sieve-rotor speed. In contrast to classical rotating-sieve systems, conical sieves offer a high material throughput already at low sieve speed values. To evaluate the sieve-speed impact on final granule size, compaction was performed at a 10-kN/cm specific compaction force, 2-rpm roller speed, and increasing sieve speed values for one screen size (i.e., 1.5-mm rasp sieve).

With higher sieve speed, the amount of fines decreased. This result can be explained by the fact that, with higher rotor speed, the ribbons need less time to pass the screen. Less friction occurs during granulation and leads to a lower amount of fines. Therefore, altering the sieve speed is another possibility to adjust the desired particle-size distribution of the final granules.


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