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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Therefore, keeping the droplet size similar is recommended during scale up. There are many that believe that atomization air pressure controls droplet size in relation to spray rate. Actually, the atomization flow rate is the actual parameter that controls droplet size. Droplet size is inversely proportional to atomization air flow rate and directly proportional to spray rate. Therefore, as the spray rate increases, the droplet size increases. As atomization air flow increases, droplet size decreases. So, in scale-up, the atomization air flow should be increased proportionally with the spray rate to keep the droplet size the same. This is expressed as follows:

AAV2= AAV1SR2/SR1

Where:
SR2= Spray rate of unit 2 (g/min)
AAV2 = Atomizing air volume of unit 2 (CFM)
SR1 = Spray rate of unit 1 (g/min)
AAV1 = Atomizing air volume of
unit 1 (CFM)

Unfortunately, the relationship between atomizing air pressure and flow is not always linear, so it is best to measure the flow on the equipment. Many fluid bed units are not equipped with atomization flow capabilities, so the next best way to determine atomization air flow is to consult the air consumption charts supplied by the nozzle vendor. These are available upon request.

PRODUCT TEMPERATURE
Product Temperature is a dependent variable that is influenced by:

• Inlet temperature
• Air volume
• Dew point
• Spray rate

Therefore, if inlet temperature and dew point remain unchanged during scale up, the product temperature should not change if the air volume and spray rate are increased proportionally. However, total dew point control is not always available, but dehumidification is more commonly seen. That means, in summer, the air is dehumidified down to a set dew point. But in the winter, if the ambient dew point is already below the set point, there is no way of increasing the humidity. This will increase drying capacity in the winter and actually show a lower product temperature and also lower product moistures. Sometimes, inlet temperature can be decreased or spray rate increased to maintain the product moisture in these cases.

DEALING WITH DIFFERENCES
The major particle characteristics that can change when scaling up a fluid bed granulation are bulk density and particle size distribution. These changes are usually not realized until the first scale-up batch is made. These changes can be handled most of the time with changing only a few parameters away from the calculated target.

For increases in bulk density, a decrease in in-process moisture and a reduction in droplet size usually can reduce the density somewhat. In production, we do not want to lengthen the process, so the atomizing air can be increased to create smaller droplets. To reduce the in-process moisture, we do not want to increase the level of fluidization (which can cause attrition), so the inlet temperature can be increased.

These changes may decrease the particle size, but usually in scale up, the particle size increases due to the mass effects. So, in essence, changing either the inlet temperature or atomizing air pressure can have profound, synergistic effects on particle size and bulk density of the product.

Finally, sometimes the particle size distribution can increase with scale up. This is mainly due to the proximity of the nozzle to the bulk of the fluidizing bed. If the distribution is too wide, the nozzle can be raised to a higher position to narrow it.

If the theoretical approach to scaling up a fluid bed granulation is followed, minimal development will be needed to reproduce the quality achieved in the R&D scale. The basis for additional optimization to rectify minor changes in particle size and bulk density can be handled in a well understood manner, based on the tips provided to modify these characteristics.

Published in the 2013 edition of Pharmaceutical Manufacturing magazine

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