Granules and Granulation Flashcards
Powders
Usually a mixture of fine powders, including active ingredient, colours, flavours and sweetening agents
Granules
Comprise powder particles that have been aggregated to from large particles sufficiently robust to withstand handling
small granules size?
0.2 to 0.4 mm
large granules size?
1 to 4 mm
define granulation:
processed to adhere to from larger multi-particulate entities
Give reasons for granulation:
Loosely packed
Poor flowability
Not uniform
Dusty
Denser
Good flowability
Uniform
Reduce dust
Why does granulation occur?
To prevent segregation of the constituents of a powder mix
Particles tend to segregate due to differences in the size, shape and density
To improve the flow properties of the powder mix
To improve compaction properties and uniformity of the mix
To reduce toxic dust
Other reasons
Reduce caking of hygroscopic materials
Increase bulk density, therefore reduce storage volume
Improve appearance of final product
Prevention of segregation
Segregation or demixing: small dense particles
to the bottom;
large less dense particles to the top
Granules prevent segregation of the constituents of a powder mix
segregation
Particles tend to segregate due to differences in the size, shape and density
Flowability
Angle of repose
“Bulk density “ (“Do” )
“weight of sample” /”volume of powder when poured into the cylinder”
“Tapped density “ (“Df” )
”=” “weight of sample” /”volume of powder after tapping until fully settled”
“Carr’s index “
“Df – Do” /”Df” “×100”
“Hausner ratio “
“Do” /”Df”
Low interparticulate friction
More cohesive powders
What is the process of wet granulation?
1) Blend powder = SOLID drug/excipients
2) moist mass = LIQUID; solvent/ binder
3) moist agglomerates = After wet massing, the moist mass is pressed through a sieve or extruder to size the granules
4) dried granules = Primary particles of granules are held together by solid bridges held together by solid bridges upon drying
Bridges of hardening binding agent
Bridges of crystallised drug or excipient
5) sized granules =
Cost, stability, los of material, multiple processing steps, incompatibilities
Granulation is an expensive process because of labour, time, equipment, energy and space requirements
may be major concern for moisture-sensitive or thermolabile drugs, as well as those exhibiting polymorphisms
during various stages of processing
add complexity and make validation and control difficult
between formulation components can be aggravated
Equipment for wet granulation
High-shear granulation - Mixing, densification and agglomeration achieved through shear and compaction force exerted by the impeller
Fluid-bed granulation - Spraying a binder solution onto a fluidized powder bed
Dry granulation
Blend powder
Slug
Granules
Sized granules
Ball growth mechanism (each process may overlap):
Coalescence > Breakage
> Layering > Abrasion transfer
