RAPID MIXER GRANULATOR (COMPILED DOC)

1. Design Qualification for Rapid Mixer Granulator (Compiled Doc)
2. Installation Qualification for Rapid Mixer Granulator (Compiled Doc)
3. Operational Qualification for Rapid Mixer Granulator (Compiled Doc)
4. Performance Qualification for Rapid Mixer Granulator (Compiled Doc)

A Rapid Mixer Granulator (RMG), also called a High-Shear Mixer Granulator, is a core granulation machine used in solid oral dosage manufacturing to convert powders into uniform, free-flowing granules suitable for compression or capsule filling. It achieves rapid, controlled granulation by combining intense mixing with high-shear wet massing inside a closed bowl.

How it works

An RMG has two main agitators:

• Impeller (main mixer): blends powders and distributes binder evenly.
• Chopper: breaks lumps and controls granule growth, improving size distribution.

Process steps typically include:

1. Dry mixing of API and excipients to achieve blend uniformity.
2. Binder addition (solution or water) through a spray/nozzle or addition port.
3. Wet massing/granulation where shear forces create granules.
4. Discharge of wet granules for drying (often in a Fluid Bed Dryer).

Key process parameters (CPPs)

• Impeller speed and time
• Chopper speed and time
• Binder type, concentration, addition rate, spray pattern
• Total binder quantity (L/S ratio)
• Granulation end-point determination (torque/power consumption trend, time, or PAT tools)
• Batch load and bowl fill level
  These parameters strongly influence granule size distribution, fines, density, flow, compressibility, dissolution, and content uniformity.

GMP and qualification focus

Because RMG is a critical process step, pharma controls include:

• Equipment qualification (IQ/OQ/PQ) and preventive maintenance (seal integrity, chopper blades, impeller clearance).
• Cleaning and cleaning validation (wet granulation residues can be sticky; attention to discharge valve, seals, chopper housing).
• Containment and dust control (closed transfer, HEPA vacuum cleaning, split-valve/IBC interface for potent products).
• In-process controls: granule LOD/moisture, sieve analysis, bulk density, and blend uniformity checks after milling.
• Batch records/data integrity: recorded setpoints, actual run parameters, deviations, and end-point evidence.

Common failures include over-wetting (large lumps), under-wetting (poor granulation), inconsistent binder spray leading to variability, and inadequate cleaning causing cross-contamination risk.