W4 Granules and Granulation (ZM) 18.10 Flashcards
What are Powders-what do they include?
Pharmaceutical example:
Usually a mixture of fine powders, including
active ingredient, colours, flavours and
sweetening agents
Ciprofloxacin powder for
suspension
What is Granulation?
2 types of granules?
Pharmaceutical example?
The process by which dry primary powders (i.e. single discrete powder particles) are processed to adhere to from larger multi-particulate entities
-
Small granules (~0.2 to 0.4 mm)
-Usually used as intermediates to be mixed with other excipients prior to tablet compaction or capsule filling -
Large granules (~1 to 4 mm)
-Often dosage forms in their own right
e.g. Ciprofloxacin granules for suspension
Why are the reasons for granulation?
Granules are denser, good flowability, uniform, reduce dust
- 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 (flowability) 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
What does hygroscopic mean?
Ability to absorb moisture from the air
What are the types of particle segregation? (3)
Sifting/percolation- when small particles go through holes within larger particles (up and down)
e.g. when putting material into a container
Trajectory- (side to side) small particles at bottom and large particles at top
e.g. in a screw conveyor
Fluidisation (up and down)- small particles at top
Dusting (side to side) e.g. in a stone pile
Angle of repose, Pyramid shape e.g. in a stone pile.
If something flows well, the angle of repose is smaller or larger?
What are the degrees for:
excellent flow?
poor flow?
… is smaller
excellent flow = 25-30°
very poor flow = >60°
What are the equations for Carr’s index or Hausner’s ratio?
Carr’s index:
(DF-Do)/Df x100
- Measure of strength and stability
Where Df= Bulk density
Do= Tapped density
Hausner ratio= Do/Df
- measure of the interparticulate friction
Tapped density:
What does a lower Cl or lower HR indicate?
(CI- Carr’s index, HR- Hausner’s ratio)
Better flow properties
What are some methods to measure the flowability of powders/granules?
- Angle of repose
2.Tapped density
What are the 2 types of granulation, what do they involve?
Wet and Dry granulation
Wet- using glue to bind powder together
Dry- no liquid, relies on cohesive properties of powder
Wet granulation- what are the 5 steps in the process?
- Blend powder in a cube shape mixer
- Add binder
- Left with moist mass- sieve
- Moist agglomerates- dry them so bridges are crystallised
- Dry granules- sieve as they could still be dif sizes, do this for quality control so they all have a mean size
- Sized granules
Binders:
What are some examples of
1. Natural binders?
2. Synthetic/semi synthetic polymers:
- Sugars/natural binders:
Sucrose
Liquid glucose
Acacia
Tragacanth
Gelatin
Starch paste
Pregelatinised starch
Alginic acid
Cellulose - Synthetic/semi synthetic polymers:
Methyl cellulose (MC)
Ethyl cellulose (EC)
Hydroxypropyl methylcellulose
(HPMC)
Hydroxypropyl cellulose (HPC)
Na-carboxymethyl cellulose (CMC)
Polyvinyl pyrrolidone (PVP)
Polyethylene glycol (PEG):
Polyvinyl alcohol (PVA)
Polymethacrylates (PMA)
What are the limitations of wet granulation? (5)
- Cost: Granulation is an expensive process because of labour, time, equipment, energy and space requirements
- Stability may be a major concern for moisture-sensitive or thermolabile drugs, as well as those exhibiting polymorphisms
- Loss of material during various stages of processing
- Multiple processing steps add complexity and make validation and control difficult
- Incompatibilities between formulation components can be aggravated
What are the different types of wet granulation? (4)
- High-shear granulation- Mixing, densification and agglomeration achieved through shear and compaction force exerted by the impeller (+chopper +binder spray nozzle)
- Fluid-bed granulation- Spraying a binder solution onto a fluidised powder bed
- Extrusion-spheronization- spheronization at edge of bowl
- Spray-drying granulation- atomiser, liquid feed, drying gas, drying chamber, cyclone, exhaust gas, dry particles collector
What are the steps in dry granulation?
- Blend powder in a cube mixer- compress. The powder mix is squeezed between two rollers and the powder is pressed into flakes (like cornflakes).
- Slug- Preparation of large tablets (slugs)
– usually 25 mm in diameter and 10 to 15 mm thick - Granules- sieve shaker
- Sized granules
