Theories and Practice on Fluid Bed Granulation

Writer： admin Time：2020-11-25 17:24 Browse：℃

Technology of fluid bed started from 1942 but was not adopted in pharmaceutical industry at that time. Later Wuster released the first report on adoption of fluid bed in pharmaceutical industry to coat tablets. As technologies developed, Wunster started its application of fluid bed in one-step granulation from 1960.
 
1. Theories on fluid bed granulation
Fluid bed granulation is particularly suitable for material whose size ranges from 50μm to 200μm. The fluidization of granules is actually the result of joint forces between granules. The strong airflow can overcome granules’ gravity and thus fluidize them. low-speed input air blows the granules at the speed directly proportional to the pressure drop in fluid bed. As the air speed increases, granules turn to suspending. At this point, the air speed is called the minimum fluidizing velocity. This velocity is a primary lower limit of one-step granulation. As granulation goes on, the velocity increases gradually. But the fluidizing speed during granulation should be higher than this minimum speed so as to not separate fine granules from large granules.
 
When fluidizing speed is higher than the minimum fluidizing speed, the fluidized material moves like being boiled. There are foams forming under the fluid bed and near the airflow distribution board. The foams can ascend and then burst due to the function of air blower. It can be thus seen that airflow distribution board can have great influence on the fluid bed. And as fluidizing speed increases, the powder expands and granule density decreases in the unit volume. Furthermore, when the fluidizing speed reaches a certain speed, the granules will be blown away. The speed at this point is referred to as entrainment velocity. The granulating and mixing degree is related to granule size and movement of airflow through the material. And the movement of airflow can also influence heat exchange between air and granules.
 
The standard air input velocity is usually 1.0-2.0m/s. For agglomerated material, the airflow rate should be five or six times higher than the minimum fluidizing velocity. During drying, the airflow rate should keep relatively low, ranging from 0.8m/s to 1.4m/s. Even though wet material in the fluid bed demands high airflow rate at the beginning of drying, the air speed should be slowed down after the products are dehydrated to guarantee granules’ normal motion and prevent material from entering the filter. Granule motion and quick drying together play an important roll in fluid bed granulation. The good granulating state is that the granules move down freely. The fluidizing state can also be monitored depending on the exhausted air temperature. Different product has its own proper drying speed. The temperature inside the fluid bed should keep constant for a pretty long time. Therefore, if the temperature of exhausted air rises more quickly than expected, the fluidization is not so good that granulation should be stopped and some manual or mechanical measures can be taken to facilitate fluidizing.
 
2. Principle on granule agglomeration and growth
Agglomeration is the process during which fine granules grow and obtain larger size. There are three principles to explain agglomeration:
 
1) The immobile liquid on the granule surface forms cohesive bridge for fine granules’ cohesion;
2) The surface force and capillary force compact granules;
3) The material once dissolved in a solvent crystallizes and forms solid bridge.
 
Ideally, the primary granules contact with moisturizer droplets while passing through the spraying area in the fluid bed. The moisturizer spreads on the granule surface and wets the granules. At the same time, granules compact to form liquid bridge. Then the granules are dried and solidified to larger granules. The granulating principle of fluid bed is as follows: