Optimization and scale-up of a fluid bed tangential spray rotogranulation process

The production of pellets in the pharmaceutical industry generally involves multi-step processing: (1) mixing, (2) wet granulation, (3) spheronization and (4) drying. While extrusion-spheronization processes have been popular because of their simplicity, fluid-bed rotogranulation (FBRG) is now being considered as an alternative, since it offers the advantages of combining the different steps into one processing unit, thus reducing processing time and material handling. This work aimed at the development of a FBRG process for the production of pellets in a 4.5-l Glatt GCPG1 tangential spray rotoprocessor and its optimization using factorial design. The factors considered were: (1) rotor disc velocity, (2) gap air pressure, (3) air flow rate, (4) binder spray rate and (5) atomization pressure. The pellets were characterized for their physical properties by measuring size distribution, roundness and flow properties. The results indicated that: pellet mean particle size is negatively affected by air flow rate and rotor plate speed, while binder spray rate has a positive effect on size; pellet flow properties are enhanced by operating with increased air flow rate and worsened with increased binder spray rate. Multiple regression analysis enabled the identification of an optimal operating window for production of acceptable pellets. Scale-up of these operating conditions was tested in a 30-l Glatt GPCG15 FBRG.