Roller Compactor and Dry Granulation

Study Notes

RCDG (Roller Compactor Dry Granulation) is a method of choice for processing moisture sensitive drugs, as no liquid binder is required.
Suitable for compounds with low melting points or degrade rapidly during heating, as it does not involve any drying step.
Ideal for processing drugs with low & inconsistent bulk and tap densities, fine and inconsistent particle sizes, poor flow properties, and compatibility issues.
Often used for densifying APIs and blends with high active loading.
Excellent for moisture sensitive products.
Continuous process, up to 600 kg/hr.
Granule size is controlled by the milling step.

Powder is fed by gravity or a screw feeder through two equal diameter counter-currently rotating rollers.
Process variables:
- Roll speed
- Screw feeder speed
- Compaction (Roll) pressure
- Deaeration pressure

Advantages:
- Useful for heat or moisture sensitive materials.
- Requires less equipment and space than wet granulation.
- Improves tablet disintegration by increasing water-uptake ability of the disintegrant.
- Suitable for effervescent tablets.
Disadvantages:
- Requires high-duty machines compared to direct compaction.
- Dry process produces more dust, potentially contaminating other drugs.
Applications:
- Used when direct compression is not applicable (e.g., large-dose or poorly compressible drugs).
- Used when wet granulation is not possible (e.g., drugs sensitive to heat or moisture).
- Common for vitamins and effervescent tablets.

Heated and filtered air is blown through the bed of unmixed powders to fluidize the particles and mix the powders.
Granulating fluid is sprayed onto the bed of powders, causing primary particles to adhere when droplets and powders collide.
Excess material is prevented from escaping through exhaust filters, periodically agitated to reintroduce collected material into the bed.
Wet granules are then dried in the heated fluidizing air stream.

Advantages:
- Relatively fast granulation.
- Good control of particle size.
- Excellent content uniformity.
- Precise temperature control.
- Includes drying step.
- May not need milling, reducing total process time and steps.
- Available in wide batch volumes (up to 8,400 liters).
- Multi-functional (drying, granulation, & coating).
Disadvantages:
- Requires a relatively high amount of granulating liquid.
- Expensive to acquire a fluidized bed granulator.

Binder solution is sprayed onto a starting powder blend inside the rotor disc to form granules.
Rotor force forms a more spherical granule than top spray methods.
Advantages:
- Superior processing control (independent airflow and product rotation).
- Precision granule sizing and coating thickness.
- Processing flexibility (low airflow for coating, spheronization, powder layering, high density granulation, and high airflow for drying).
- Relatively fast granulation, spheronization, and powder layering.
- Produces very uniform particle size, not requiring milling.
- Includes the drying step.
- Capable of producing spherical dense granules.
Disadvantages:
- More complex process than top spray.
- Smaller batch sizes compared to other methods (less than 500 liters depending on the process).

Top spray and GXR density examples:
- Tryptophan: Unprocessed (0.13 g/cc), Top-spray (0.24 g/cc), GXR (0.43 g/cc).
- Sulfamethazine: Unprocessed (0.31 g/cc), Top-spray (0.43 g/cc), GXR (0.60 g/cc).
- Lactose: Unprocessed (0.50 g/cc), Top-spray (0.49 g/cc), GXR (0.60 g/cc).
- Ascorbic Acid: Unprocessed (0.46 g/cc), Top-spray (0.56 g/cc), GXR (0.63 g/cc).
GXR Spherical Granulation Reasons:
- Creates a very narrow particle size distribution (PSD).
- Granules are much more spherical than other methods.
- Achieves excellent content uniformity from granule to granule.

Ibuprofen pellets were generated using a GRANUREX® rotor processor, converting 7µm poorly flowing powder to 250µm granules with excellent flow characteristics.
Ending product characteristics:
- 250 micron spherical pellets.
- 0.59 g/cc density.
- Very good flow properties.