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

Area of Science:

• Pharmaceutical Manufacturing
• Process Engineering
• Materials Science

Background:

• Traditional pellet production involves multiple sequential steps: mixing, wet granulation, spheronization, and drying.
• Extrusion-spheronization is a common method, but fluid-bed rotogranulation (FBRG) presents an integrated alternative, reducing processing time and material handling.

Purpose of the Study:

• To develop and optimize a fluid-bed rotogranulation (FBRG) process for pharmaceutical pellet production.
• To identify key process parameters influencing pellet physical properties.
• To establish an optimal operating window for FBRG and validate scale-up.

Main Methods:

• Utilized a 4.5-l Glatt GCPG1 tangential spray rotoprocessor for pellet development.
• Employed factorial design to optimize parameters: rotor disc velocity, gap air pressure, air flow rate, binder spray rate, and atomization pressure.
• Characterized pellets by measuring size distribution, roundness, and flow properties.

Main Results:

• Pellet mean particle size was negatively impacted by increased air flow rate and rotor speed, but positively by binder spray rate.
• Improved pellet flow properties were observed with higher air flow rates, while increased binder spray rates worsened flow.
• Multiple regression analysis identified an optimal operating window for producing acceptable pellets.

Conclusions:

• The study successfully developed and optimized an FBRG process for pharmaceutical pellet production.
• Key parameters influencing pellet characteristics were identified, allowing for targeted control.
• The optimized FBRG process demonstrated successful scalability to a larger 30-l GPCG15 unit.