Comparison between mixergranuiators

Figure 19 shows the effect of moisture content upon mean granule size when granulating calcium hydrogen phosphate with a PVP-PVA copolymer solution. With the Fielder mixer, considerably less liquid is required to achieve a certain granule size than with the Lodige mixer. In addition, the impeller rotation speed affects the liquid requirements. Examination of the porosity changes during the process shows that the Fielder mixer is more efficient at densifying the agglomerates, and that the resulting low porosity is associated with a corresponding low liquid requirement. The effects of the different liquid requirements and porosities are cancelled out by plotting granule size against liquid saturation. The resulting graph coincides with the correlation shown in Fig. 12.

When the Fielder mixer was operated with an impeller speed of 500 r.p.m., the agglomerate porosity was reduced to about 20% which gave rise to overwetting of the mass and, consequently, uncontrolled growth, as indicated by the dotted lines. This demonstrates the potential risk for 'overgranulation' or overwetting by wet granulation in high shear mixers of cohesive powders which consolidate steadily during the process. A change in porosity of, say, 2% produces a change in liquid saturation of about 10%, c.f. equation 13, which in the stage of rapid growth by the coalescence mechanism may turn the process into uncontrolled growth.

Schaefer etal. (1986b, 1987) compared different high shear mixers available in the Danish pharmaceutical industry. The comparison was based on wet granulation of calcium hydrogen phosphate. The different growth rates obtained in the different mixers could be attributed to differences in intensity of agitation, as expressed by the swept volume. Surprisingly, scaling up from laboratory to production scale mixers had only a minor effect on the liquid requirements.

Richardson (1982) characterized the impellers in different high shear mixers by their relative swept volumes. The vertical volume swept out by the impeller blades at each revolution is calculated by dividing the blade area into vertical segments. On the basis of this volume and the impeller speed, the volume swept out per second can be calculated and divided by the volume of the mixer bowl in order to obtain the relative swept volume. The relative swept volume thus depends on the vertical dimensions of the impeller blade, on the impeller speed, and on the size of the bowl. The relative swept volume is a measure of the energy input of the impeller blades on the material. Accordingly, a higher relative swept volume was found to result in a greater increase of the product temperature and in denser granules when comparing high shear mixers of different type (Schaefer, 1988).

Table 2 compares Diosna and Fielder mixers of different scale. In the

Table 2 The relative volume swept out by the impeller in Fielder and Diosna mixers of different scale (Schaefer, 1988)

r.p.m.a

Relative swept volume per second11

Diosna P 25

150/300

1.37/2.74

Diosna P 50

144/188

1.08/2.16

Diosna P 250

95/190

0.52/1.03

Diosna P 400

65/130

0.36/0.72

Fielder PMAT 25

150/300

0.75/1.51

Fielder PMAT 65

150/300

0.71/1.42

Fielder PMAT 150

127/254

0.61/1.23

" Low/high impeller rotation speed.

" Low/high impeller rotation speed.

Diosna mixers, scaling up results in a marked decrease in the relative swept volume and consequently in a lower power input. As a consequence, the resulting granule porosity increases in scaling up. Richardson (1982) showed that the fall in relative swept volume can be compensated for by a longer wet massing time in production-scale mixers, thereby obtaining denser granules. An alternative is to change the relative swept volume by modifying the impeller design or by variation of the impeller speed. The latter method is questionable if it results in a significant difference in the centrifugal forces in the different mixers.

Table 2 shows that there is only a slight decrease in relative swept volume when scaling-up in Fielder mixers. In laboratory and pilot scales the relative swept volume is higher in Diosna mixers than Fielder mixers. Accordingly, Schaefer etal. (1987) found that the Diosna mixers produced denser granules than did the Fielder mixers. They observed no significant differences between the Diosna P 250 and Fielder PMAT 150 where the swept volumes are similar.

Direct scaling up of the amount of binder solution by adding the same relative amount on different scales does not lead to a constant moisture content in the mass. The marked heat production, caused by the high power input in high shear mixers, results in the evaporation of water which is pronounced in the small mixers because of the more intensive agitation. In extreme cases, the loss of water may account for more than 15% of the amount added (Kristensen, 1988a). In the study by Schaefer etal. (1986b, 1987), this meant that approximately the same amount of binder liquid was required in small- and large-scale mixers. When scaled up the reduced evaporation of water compensated for the higher intragranular porosity so that the liquid saturation level was kept almost constant.

An attempt to identify the parameters of scaling up has recently been presented by Horsthuis etal. (1993) who compared wet granulation of lactose in three high shear mixers (Gral 10, 75 and 300). The three mixers are not geometrically similar. The relative swept volume is, therefore, strongly dependent on the mixer scale. It was found that the granulation process with respect to temperature increase and granule size distribution could be scaled up by keeping the Froude number constant. The dimensionless Froude number expresses the value of N2D/G where N is the revolutions per minute, D is the diameter of the impeller and G is the gravitation constant. The Froude number is the ratio of the centrifugal force to the gravitational force. In their experiments, a constant relative swept volume or a constant impeller tip speed did not result in a comparable process. This particular study demonstrates that the relative swept volume is insufficient to predict scaling up when there is a large difference in scale between the different mixers. The centrifugal forces should also be kept approximately constant in addition to the relative swept volume in order to achieve comparable processes in the scaling up. A variation in centrifugal forces means that the part of the impeller blades which is effective in wet massing also varies.

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