Granulation Flashcards
Granulation Outline
If particles are too small for tableting, add liquid to collect them together into bigger substance (granules)
Granulation Function
prevent powder segregation, improve powder flow, improve compaction and reduce airborne powder (safety, less cross contamination)
Granulation Methods
Dry, wet and hot melt
Dry Granulation Outline
High pressure aggregation. 2 methods: slugging and compaction
Slugging Outline
Powders are compressed into large tablets and then broken down into smaller powders
Roller Compaction Outline
Powder pressed into sheet between 2 rollers. Milled into granules
Wet Granulation Outline
Aggregation using granulating fluid (liquid binder) which is removed in the subsequent drying step
Granulating Fluid Outline
non-toxic volatile solvent. Eg water, ethanol, isopropanol
Dry Granulation Steps
Mixing, application of pressure, milling, separation of particle size and mixing
Wet Granulation Steps
Mixing, adding granulation fluid, agitation, drying, milling particle size separation and drying
3 Stages of Granulation
Nucleation, Transition and Ball Growth
Nucleation Outline
2 particles clump together due to liquid bridges
Transition outline
Nuclei grow bigger by forming more liquid bridges between themselves and other particles/nuclei
Ball Growth Outline
Large spherical granule growth. Needs to be monitored to prevent unusable mass formation
Granulation bonding mechanisms
adhesive/cohesive forces in immobile liquids, interfacial forces in mobile liquids, solid bridge formation, dry granulation attractive forces and mechanical interlocking
Adhesive/cohesive forces in immobile films
Film decreases space between particles, increasing the effect of Van der Waal forces
Interfacial forces in mobile films Outline
Interactions between powder particles and granulating fluid. Granulating fluid spreads between particles gradually from dry state to pendular (rings), funicular (spread) and capillary (liquid suction at interface). liquid bridges replaced with solid
Solid Bridge Formation Outline
Binding agent in solvent solidifies (crystallisation). Slower rate of drying = larger crystals
Attractive forces in dry granulation
Van der Waals and electrostatic forces
Granulating Equipment
Shear granulators, high-speed mixer-granulators, fluidized bed granulators, roller grinder, spherisers/pellitisers and spray dryers
High Speed Mixer and granulators Outline
Powders added to bowl and mixed with impeller. Granulating fluid added to bowel. Liquid mixed into powder to form a moist mass. Chopper cuts moist mass into granules (usable masses). Granules discharged
High-speed mixer-granulators advantages
mixing and granulation at once, can take large volumes (used in industry) and fast (formed in minutes)
High-speed mixer-granulators disadvantages
Can form over-massed unusable granules and sensitive to raw materials variations
Fluidised Bed Granulators
Mixing, granulation and drying. Filtered air blown through powdered bed (mixing), granulating fluid sprayed above powder bed (fluidised), heated air blows through to dry and granules are discharged. Often used just for drying (less variables need control)
Fluidised bed granulators Advantage
Multipurpose, large amounts at a time and mixing by fluidation is very efficent
Fluidised bed granulators disadvantages
expensive equipment, not suitable for thermosensitive and parameters must be changes often for each drug types
Why is roller compaction preferred over slugging
Pressure application is more gentle for roller (less energy). Slugging particles have poor recompaction properties after granulation
Roller Compaction Outline
Powder fed through 2 counter rotating rollers. Powder passing through rollers is pressed into sheet. Advantages: versatile (eg easy to modify flow rate) and easy to scale up (large vols and economical)
Palletisation/Spheronisation Outline
Spherical agglomerate forming (for controlled release formation).
Spheronisation Advantahge and Disadvantage
Advantage: produces many different types of sphere. Disadvantage: labour intensive
Extrusion Def
Force wet mass through die of different dimensions. Shapes powder into different cylindrical particles with uniform diameters. Powder must undergo plastic deformation. Distinct mechanism feeding powder into die
Spheronisation Def
Rounding of rods formed in extrusion using frictional forces
