Scaling up of the fluidized bed granulation process.
The scaling up of a fluidized bed granulation process from small scale to production scale is often done empirically in the pharmaceutical industry. In this study, a more practical and systematic method was developed in order to achieve a similar granule size in the scaled up fluid bed. The scaling up is based on the relative droplet size, and the powder bed moisture content at the end of the spraying cycle. The present study describes the scaling up of the fluidized granulation process from small (5 kg scale) to medium (30 kg scale) and to production fluid bed scale (120 kg scale). The granulation process is scaled up with as target a geometric mean granule size of 400 microm. First, the effect of the relative droplet size on the granule size was investigated in the different fluid beds. The effect of the change in relative droplet size on the granule size was different for each fluid bed. Second, experimental design is applied on the small and the medium fluid scale, and regression models for the granule size are proposed in order to scale up the granulation process on the small to medium scale. The granulation process was also successful by scaling-up to the large fluid bed, considering only the relative droplet size.
Rambali
B
B
Farmaceutisch Instituut, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090, Brussels, Belgium. bisoen.rambali@rivm.nl
Baert
L
L
Massart
D L
DL
D011208:Powders; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*
D011208:Powders