granulaiton Flashcards
wet agglomeration
wet massing by planetary or HSM, extrusionand pelletization
agglomerate growth through continuous agitation
balling, fluid bed
LSM
humidification and vacuum drying
types of granulation method
1) direction compression
2) wet granulation —-> sphere
3) dry granulation
4) thermoplastic granulation –> sphere
particle size of primary component
compare particle size
smaller particles requires higher amount of binding liquid than larger particles,
because
smaller particle usually more difficult to densify to due higher packing density and SA higher
component particle size on end product
smaller particles are favored in producing agglomerates that are more spherical, with smoother surfaces and of narrower size distributions
smaller particles also generally produce stronger agglomerates
packing properties affected by
particle shape
irregular shape cr8 interlocking among particles and thus increase agglomerate strength whereas a rounder particles reduces the strength
Direct compression
advantage and prerequisit
1) most effective and efficient method to prepare free flowing powders for tableting, mix and blend, without the additional step to increase particle size
requires material w
- suitable flow
- narrow size distribution
- minimal segregation and good compressibility
major advantage of dry granuatin by roller compaction wet granulation methods
- few unit processes ,thus lower production cost
- suitable for heat and or water sensitive material
- a feasible process for preparing controlled release product
bonding mechansim in dry granulation
1) particle rearrangement
2) particle fragmentation
3) particle bonding
adv roller compaction
1) simple direct processing
2) eliminates granulating solvent
3) less energy and manpower to operate
4) allows continuous manufacturing
5) useful for heat/moisture sensitive products
5) vacuum to suck air , air can cause breaking??
critrical operation attribution for roller compaction
1) screw feed rate
2) roll speed
3) roll pressure
4) roll gap
compaction zone
1) slip region
particle begin slipping at the roll surfaces, some plastic
deformation of solid occurs
2) nip angle region
densification occur
3) release region:
immediate after powder compaction, size depends on extend of powder’s (compact’s) elastive recovery
factors affecting compact strength
1) applied pressure
2) extend of air entrapment (use vacuum system)
3) roll dwell time
4) powder void fraction (space into which air is compacted)
5) particle size of component and density
6) type of binders included
7) moisture content of material
purpose of wet granulation
1) improve flow properties
2) reduce bulk volume, densification
3) improve compression properties
4) improve distribution of a minor constituent eg low dose drug binder, colorant
5) prevent components from segrating
6) reduce dust
7) minimise or mitigate adverse properties of API
eg hydrophobicity, bad taste, poor stability
disadv of wet granulation
1) additional processing steps, adds complexity, cost, extra validation work
2) additional time and space needed
3) unsuitable for moisture-sensitive or thermolabile drgs
4) material loss due to additional processing steps
types of LSM and HSM
LSM
planetary mixer
orbiting
HSM
HSG
low mean particle size + wide size distribution
pack well and high strength
mechanism
1) nucleation
2) coalescence
large paricle size + narrow size distributino
low strength
mechanism
1) nucleation
2) layering
Main granule growth mechanism
- nucleation
- coalescence
seconfary growth mechanisms
- layering from degradation of existing particles
- ball growth
requirements for successful granulation
1) dissolution of solids by solvent, and later the solute forms crystaline bridges when dried
2) dissolved binder in the granulating liquid may also by responsible for the formation of solid bridges
3) solid bridge formed the binding structure between particles
if solid bridges are absent, granules will revert back to the original powder
Process steps of granulation by HSM
1) mixing of dry powder at high impeller speeds for 2-5min
2) additional of liquid binders, lower speeds, 1-2min
3) wet massing, high speeds, 1-5min
4) wet sieving of granules usually using cone mill
5) drying usually by fluid bed dryer
6) regranulation by cone mill
adv of HSM granulaiton
1) short process time
2) less binder needed, therefore, shorter drying time
3) suitable for cohesive materials as well dense production
4) less sensitive to raw material physical attributes than fluid bed granulation
5) closed system: GMP, possibility for vacuum, microwave drying
6) easy to clean, CIP possible
problems associated with HSM granualtors
1) mechanical degradation of weak powders and granules
2) some heat generation, unsuitable for thermolabile products
3) risk of over-wetting leading to uncontrolled growth.
process variable for HSM
1) Impeller rotation speed (tip speed)
2) chopper rotation speed
3) load
4) liquid addition method
5) liquid addition rate
6) wet massing time
