Focused beam reflectance method as an innovative (PAT) tool to monitor in-line granulation process in fluidized bed.

Fluidized bed granulation is a commonly used unit operation in the pharmaceutical industry. But still to obtain and control the desired granule size is challenging due to many process variables affecting the final product. Focused beam reflectance measurement (FBRM, Mettler-Toledo, Switzerland) is an increasingly popular particle growth analysis technique. FBRM tool was installed in two different locations inside a fluidized bed granulator (GPCG2, Glatt, Binzen) in order to monitor the granulation growth kinetics. An experimental design was created to study the effect of process variables using FBRM probe and comparing the results with the one's measured by sieve analysis. The probe location is of major importance to get smooth and robust curves. The excess feeding of binder solution might lead to agglomeration and thus to process collapse, however this phenomenon was clearly detected with FBRM method. On the other hand, the process variables at certain levels might affect the FBRM efficiency by blocking the probe window with sticky particles. A good correlation was obtained (R(2) = 0.95) between FBRM and sieve analysis mean particle size. The proposed in-line monitoring tool enables the operator to select appropriate process parameters and control the wet granulation process more efficiently.