Bring Fluid Bed Granulation Up to Scale

Scaling up commercial manufacturing with the same quality and results

By Edward J. Godek, Manager, Process and Technical Operations, Glatt Air Techniques Inc.

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f = fill level (%)

Product Moisture Profile
In general, product moisture profiling during spray and drying phases is recommended in order to fully understand and replicate product quality attributes. Product moisture data should be collected at regular intervals throughout the process both during development and scale-up. The manner in which this data is generated should remain constant throughout scale up activities. Common moisture measurement methods are:
• Loss on Drying (LOD)
• Karl Fisher
• Near Infrared Spectroscopy

Moisture profiles developed on lab scale or pilot scale should be reproduced during scale up. Using the techniques described should result in target scale up parameters that will generally achieve a reproduction of a moisture profile. As an example, two batches were granulated on a Glatt GPCG-5 (batch size = 4 kg) with similar process parameters. The process was scaled to a Glatt GPCG-60 (batch size = 60 kg), where process parameters were selected to approximate the moisture profiles achieved on the GPCG-5. The measured moisture profiles and particle size distribution for each batch is shown in the charts in Figures 4 and 5. It is clear that the two GPCG-5 batches exhibited similar moisture profiles and, in turn, similar particle size distributions. Since the moisture profile maximum was lower on the GPCG-60, the particle size was slightly smaller.















Air Volume
In order to maintain fluidizing velocity at the bottom screen (or air distribution plate), air volume is scaled up using the cross sectional area of the bowl bottom screens as follows:

Calculate the area of the bottom screens:
A= πr2

A = Bottom screen area (m2)
r = radius of bottom screen (m)


AV2= AV1 A1/A2

A1 = Bottom screen area of unit 1 (m2)
A2 = Bottom screen area of unit 2 (m2)
AV1 = Air volume of unit 1 (cfm)
A2 = Air volume of unit 2 (cfm)

As mentioned earlier, the calculated air volume is a good starting target, but it may be adjusted throughout the process to maintain fluidization. Other factors also considered when selecting an air volume are:

• Bed Depth – In granulation processes, the scale-up calculations assume that the bed depth from one unit to the next remains constant. In an effort to design reasonable equipment and maximize production batch sizes, the bed depth usually increases with scale. This is not necessarily a linear relationship with the scale-up parameters and, many times, parameters such as air volume must be adjusted from the calculated value based on visual observation.

• Wall Effects – When scaling up a granulation process, many times the geometry of the larger units are such that the ratio of area of the product contact surfaces (walls) to the overall air flow and mass reduces, thereby altering the way in which the air flows through the unit. So, due to the differences in wall friction and drag, the velocity profile of the air through a larger unit is much flatter than that through a smaller unit as shown in Figure 6. This “flattening” of the velocity profile usually results in a slugging effect of fluidized product, as opposed to the smoother fluidization seen in smaller units with a sharp velocity profile.

• Mass Effects – Due to the overall increase in mass and bed depth, and the “slugging” nature of fluidization in larger units, the final granulation can be compacted and result in less porous, dense granules.















If equipment capabilities allow, inlet temperature and dew point should remain constant at each scale. In some cass, such as when a radically different air flow is needed on the larger scale, inlet temperature and dew point can be adjusted to maintain drying capacity. Also, if the product is heat sensitive, it is possible to reduce inlet temperature and dew point to maintain a required product temperature.












In order to reproduce product quality attributes achieved in development, the relative evaporation rates and moisture uptake rates of the product need to be duplicated in scale up. Since it is recommended to keep inlet temperature and dew point constant during scale up, the evaporation capacity is therefore determined by the increase in air volume only. Therefore, the spray rate needs to be scaled up to the same proportion as the air volume to maintain relative evaporation rates and moisture profiles. The calculation is a straightforward ratio:


SR2 = Spray rate of unit 2 (g/min)
AV2 = Air volume of unit 2 (CFM)
SR1 = Spray rate of unit 1 (g/min)
AV1 = Air volume of unit 1 (CFM)

In many cases, the droplet size of the sprayed binder can influence product attributes such as particle size and density. The chart in Figure 7 shows the shift in particle size distribution of two granulation batches produced on a GPCG-5. The only difference in process parameters was atomization air pressure.

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