Tableting II Flashcards
What is granulation?
primary powder particles are made to adhere to form larger, multiparticle entities called granules.
Rationale (the reason) for granulation:
Prevent segregation of the constituents of powder mix
Improve the flow properties of the mix (particle size enlargement)
Improve the compaction characteristics of the mix (binder)
Reduce the dust that may arise when handling powders (wet granulation not dry)
Hydrophobic surfaces are made hydrophilic by use of a hydrophilic binder
Wet granulation manufacture
Powder blend (add binger solution)—> moist mass (pass through screen) —> moist agglomerates(dry) —> dried granules (pass through screen) —> properly sized granules
Granule formation - wet granulation
nucleation > transition > ball growth (pendular, funicular, capillary, droplet)
Disadvantages of Wet Granulation
Quality: Affects disintegration time
Cost: Granulation is an expensive process because of labor, time, equipment, energy and space requirements
Loss of material during various stages of processing
Stability may be major concern for water-sensitive or thermo-labile drugs (alcohol may be possible)
Multiple processing steps add complexity and make validation and control difficult
Incompatibilities between formulation components can be aggregated
What are the different techniques in wet granulation
High shear mixer granulator, fluid bed granulator, marumerizer (extrusion spheroniser), spray dry granulation
explain High shear mixer granulation
Blending and wet massing is carried out using an impeller and a chopper. Mixing, densification and agglomeration are achieved through shear and compaction force exerted by the impeller.
advantages of high shear mixer granulation
Advantages:
Short processing time:
Mixing: 2 min
Granulation: 8 min
Discharge: 1 min
Less liquid binder is required
compared with fluid bed
granulation
Highly cohesive material can
be granulated
Fluid bed granulation - what is it
Fluid bed granulation is a process by which granules are produced in a single step by spraying a binder solution onto a fluidized powder bed.
Advantages and disadvantages of fluid bed granulation
Advantages:
Single step process (saving labour cost, transfer loses and time)): mixing, wet massing, granulating & drying
Homogenous particles
2-6 times greater heat transfer than tray dryer
Uniform drying… prevent mottling.
Free flowing powders
Disadvantages:
Expensive (multistep process)
Filter clogging
Generation of static electricity charges
(Accosiated) Solvent explosion
Extrusion Spheronization (e.g. the Marumerizer) - what is it
Have a Wet mass containing drug, diluents and binder is fed to an extruder to obtain rod shaped segments.
The segments are placed in the Marumerizer where they are shaped into spheres by centrifugal and frictional forces produced by rotating plates / blades and form granules.
Advantages of the marumerizer
Granules with regular size & shape with lower friability -> reduced amount of fines.
Spray drying granulation - explain it (wg)
A granulation technique that converts liquids into dry powders in a single step. This method removes moisture instantly.
Advantages of spray drying granulation
Rapid process
Ability to be operated continuously
Suitable for heat sensitive products
Spherical particles
the problems in drying in wet granulation- Consequences of solute migration
Loss of active ingredient
Mottling of coloured tablets
Intragranular migration of colour
To reduce mottling, use insoluble colour (aluminum lake)
Dry granulation what is it
Dry granulation uses mechanical compression by means of:
- Slugging press (slugs) OR BY
- Roller compaction (flakes) to facilitate the agglomeration of dry powder particles.
Draw diagram for dry granulation
WHITEBOARD!
Dry granulation is. used when
Effective dose of drug is too high for DC (DIRECT COMPRESSION)
Drug is sensitive to heat or moisture or both (so no wet granulation)
Advantages and disadvantages - dry granulation
Advantages
Ideal for moisture sensitive material
Ideal for heat sensitive material
Ideal for improved disintegration (no binder)
Disadvantages
Requires a specialized heavy duty tablet press / or a Roller compactor to form slugs
Poor color distribution uniformity in some cases
Tends to create more dust, increasing the potential of contamination
Stages in tablet manufacturing
FILL COMPRESS EJECT
Tablet Presses
Single punch press (AKA Eccentric press) [R&D]
Rotary press [production]
Hydraulic press [research]
Single-Punch Press
One die and one pair of punches
Position of lower punch determines the fill weight
Lower punch stationary during compression
Pressure determined by upper punch displacement
Tablet output 50 - 100 tablet / minute.
Manesty F
Draw diagram for single punch press
WHITEBOARD!
Rotary Press
TABLET OUTPUT?
NUMBER OF DIES?
10,000 TABLETS / MINUTE
N. OF DIES = 2-60
