Fig. 3. Impact of spray rate and Tin on RHbed and Tbed
Fig. 1. Top spray fluid bed granulation
combination of three processes including: 1) wetting, 2) aggregation and granule growth and 3) granule breakage and
attrition. There are a number of independent variables controlling the process and thus granule characteristics: fluidizing air flow rate, atomizing air pressure, inlet temperature
(Tinlet fluidizing air), inlet air humidity (RHinlet fluidizing
air), and binder addition rate (spray rate).
With this number of variables, it is desirable to simplify
the experimental space so that experiments can be designed
efficiently. In order to do so, an understanding is needed of
the underlying phenomena affecting the granule formation.
Fluid bed granule properties are primarily influenced by factors that affect granule growth, attrition and drying such as
the binder droplet and granule drying rates. These rates are
a direct result of local conditions (temperature and humidity), that cannot be directly modified or measured. They can,
however, be approximated by bed temperature (Tbed) and
bed relative humidity (RHbed), which are readily measured.
This approach is most applicable when the materials used
are not significantly hydroscopic, so there is a direct relationship between the independent variables and relative humidity
of the bed ( i.e. a small moisture accumulation term).
The elegance of this approach is that it takes four of the five
independent variables mentioned in the previous paragraph
(all except atomizing air pressure) and collapses them into two
dependent variables that can be used to describe the process
conditions and be used subsequently for optimization (Fig 2).
Fluidized bed granulation is a widely used unit oper- ation in the pharmaceutical industry as part of the process train used to manufacture solid dosage forms. The process involves spraying of a binder
liquid onto a bed of fluidized powder particles to form granules (Fig. 1). The wetted particles collide with one another
and aggregate to form larger, uniformly-sized, permanent
granules. The granules are dried (in the fluid bed) and then
subsequently used to formulate solid dosage forms.
In general, fluid bed granulation can be viewed as a
■ By S. Closs, Patheon and J. Schockey, Green Ridge Consulting
How to optimize your fluid bed granulation process for poorly compressible APIs
■ 32 JULY/AUGUST 2014 | PHARMACEUTICAL PROCESSING
■ PHARMPRO. COM
Figure 2. Effect of variables on local conditions during fluid bed granulation
Independent Impact Dependent Represent Local Impact Granule
variables variables conditions properties
Bed humidity Granule