July 29, 2021: Pharmaceutical Interview Questions and Answers
#Granulation #GranulatorOperatingPrinciples #EquipmentClassificationsForGranulation
1. What is Granulation
Granulation is the process of creating granules. The powder morphology is modified through the use of either a liquid that causes particles to bind through capillary forces or dry compaction forces.
The process will result in one or more of the following powder properties:
Enhanced flow;
Increased compressibility;
Densification;
Alteration of physical appearance to more spherical, uniform, or larger particles;
And/or enhanced hydrophilic surface properties.
2. What are the Operating Principles of different Granulation?
| Types of Granulation | Operating Principles |
| Dry Granulation | Dry powder densification and/or agglomeration by direct physical compaction. |
| Wet High-Shear Granulation | Powder densification and/or agglomeration by the incorporation of a granulation fluid into the powder with high-power-per-unit mass, through rotating high-shear forces. |
| Wet Low-Shear Granulation | Powder densification and/or agglomeration by the incorporation of a granulation fluid into the powder with low-power-per-unit mass, through rotating low-shear forces. |
| Low-Shear Tumble Granulation | Powder densification and/or agglomeration by the incorporation of a granulation fluid into the powder with low-power-per-unit mass, through rotation of the container vessel and/or intensifier bar. |
| Extrusion Granulation | Plasticization of solids or wetted mass of solids and granulation fluid with linear shear through a sized orifice using a pressure gradient. |
| Rotary Granulation | Spheronization, agglomeration, and/or densification of a wetted or non-wetted powder or extruded material. This is accomplished by centrifugal or rotational forces from a central rotating disk, rotating walls, or both. The process may include the incorporation and/or drying of a granulation fluid. |
| Fluid Bed Granulation | Powder densification and/or agglomeration with little or no shear by direct granulation fluid atomization and impingement on solids, while suspended by a controlled gas stream, with simultaneous drying. |
| Spray Dry Granulation | A pumpable granulating liquid containing solids (in solution or suspension) is atomized in a drying chamber and rapidly dried by a controlled gas stream, producing a dry powder. |
| Hot-melt Granulation | An agglomeration process that utilizes a molten liquid as a binder(s) or granulation matrix in which the active pharmaceutical ingredient (API) is mixed and then cooled down followed by milling into powder. This is usually accomplished in a temperature controlled jacketed high shear granulating tank or using a heated nozzle that sprays the molten binders(s) onto the fluidizing bed of the API and other inactive ingredients. |
| Melt Extrusion | A process that involves melting and mixing API and an excipient (generally a polymer) using low or high shear kneading screws followed by cooling and then milling into granules. Thermal energy for melting is usually supplied by the electric/water heater placed on the barrel. Materials are either premixed or fed into an extruder separately. Melt extruder subclasses primarily are distinguished by the configuration of the screw. • Single screw extruder • Twin screw extruder |
3. Equipment Classifications used for granulation.
| Equipment type | Sub classification description | Sub classification |
| Dry Granulator | Dry granulator subclasses primarily are distinguished by the densification force application mechanism. | • Slugging • Roller Compaction |
| Wet High-Shear Granulator | Wet high-shear granulator subclasses primarily are distinguished by the geometric positioning of the primary impellers; impellers can be top, bottom, or side driven. | • Vertical (Top or Bottom Driven) • Horizontal (Side Driven) |
| Wet Low-Shear Granulator | Wet low-shear granulator subclasses primarily are distinguished by the geometry and design of the shear inducing components; shear can be induced by rotating impeller, reciprocal kneading action, or convection screw action. | • Planetary • Kneading • Screw |
| Low-Shear Tumble Granulator | Although low-shear tumble granulators may differ from one another in vessel geometry and type of dispersion or intensifier bar, no low-shear tumble granulator subclasses have been identified. | • Slant cone • Double cone • V-blender |
| Extrusion Granulator | Extrusion granulator subclasses primarily are distinguished by the orientation of extrusion surfaces and driving pressure production mechanism. | • Radial or Basket • Axial • Ram • Roller, Gear, or Pelletizer |
| Rotary Granulator | Rotary granulator subclasses primarily are distinguished by their structural architecture. They have either open top architecture, such as a vertical centrifugal spheronizer, or closed top architecture, such as a closed top fluid bed dryer. | • Open • Closed |
| Fluid Bed Granulator | Although fluid bed granulators may differ from one another in geometry, operating pressures, and other conditions, no fluid bed granulator subclasses have been identified. | No sub class |
| Spray Dry Granulator | Although spray dry granulators may differ from one another in geometry, operating pressures, and other conditions, no spray dry granulator subclasses have been identified. | No sub class |
| Hot-melt Granulator | Although, hot-melt granulator may differ from one another in primarily melting the 455 inactive ingredient (particularly the binder or other polymeric matrices), no 456 subclasses have been identified at this time. | No sub class |
4. What is integrated unit as per SUPAC?
When a single piece of equipment is capable of performing multiple discrete unit operations (i.e. mixing, granulating, drying), the unit was evaluated solely for its ability to granulate. If multifunctional units were incapable of discrete steps (fluid bed granulator/drier), the unit was evaluated as an integrated unit.
Source: fda.gov
