Pharmaceutics: Granulation Flashcards
What is the BP definition of a granule?
A solid, dry aggregate of powder particles sufficiently resistant to withstand handling. They are intended for oral administration.
What are the types of granules?
Effervescent, coated, gastro-resistant, modified release
Typical size of granules are?
200um to 4mm
What are granules of 200-500um size used for?
Intermediate pharmaceutical products e.g. to become a tablet or capsule
What are granules of >500um size used for?
They form a dosage form in their own right.
What are the benefits of granules?
1) They improve powder flow, mixing and general handling
2) prevent segregation
3) improve compaction characteristics
4) reduce fines
5) increase bulk density (as more air spaces between powder particles.
What are the drawbacks/cons with using granules?
1) They involve the addition of other processing steps which increase operational costs and time spent creating dosage form.
2) They increase the instability of powder during granulation as it involves adding water and dry (both of which cause instability by affecting the powder characteristics/properties)
What is the aim of the granulation process?
To aggregate particles to form granules. So in essence particle size is enlarged.
Three necessities for making granules?
1) Powder ingredients
2) Binding solution/powder
3) Granulator
What are the two types of granulations?
Wet and dry
What are the four stages of the granulation process?
1) Mixing
2) Aggregation
3) Drying (if it’s wet granulation)
4) Sieving
Types of binders used in wet and dry granulation?
Wet: solution binders e.g. amorphous polymers as they can easily be deformed due to their lack of a lattice structure, making it easy to fluidised.
Dry: solid binders
What is a binder?
An inter-particle glue. It sticks the powder particles together for form an aggregate
What affects the solubility of a granule?
The type, amount and solubility of the binder used.
Explain stage 1 of wet granulation?
- Wetting and nucleation.
Particles are wetted by binder solution forming a nuclei. The size of the nuclei corresponds to the droplet size of the binder solution which is sprayed to ensure uniformity of particle mixture.
Explain stage 2 of wet granulation?
- Consolidation and Coalescence.
Other particles collide with the nuclei and deform and adhere to the nuclei.
Important parameters to consider with stage 1 of wet granulation?
- droplet size
- wetting properties (e.g. surface tension of binder)
- particle flux in wetting zone
Important parameters to consider with stage 2 of wet granulation?
- particle surface and moisture
- particle hardness (resistance to deformation)
- particle velocity
Important parameters to consider with stage 3 of wet granulation?
- particle velocity
- granule porosity
Explain stage 3 of wet granulation?
- Attrition and breakage.#
Fine particles shed from dry granule surface and dry granules break up
How does a high-shear mixer granulator work?
1) put dry mixing powder in the instrument
2) as this is mixed, the binder is sprayed into the instrument
3) A counter-flow system is set up as there are two rotating blades which rotate adjacently to each other.
Problems with using the High-shear mixer-granulator
can elevate temperature which can cause solvent evaporation or formulation instability.
How does a Fluidised-bed granulator work?
1) charging process: particles added into instrument
2) Fluidisation: particles are suspended by air-flow in an enclosed vessel (charging process)
3) binder solution is sprayed on to the suspended particles
4) granules form as particles collide
5) granulation, coating and drying possible
Three means of spraying the binder in the fluidised-bed granulator
top, side and bottom sprays
can watch videos linked in lecture
Why is dry granulation used?
for substances that can’t be wetted (e.g. due to being heat or moisture sensitive)
What are the two stages of dry granulation?
1) powder compaction
2) Milling
What does milling do?
Reduce particle size
Explain the process of slugging?
Loose tablet are produced by light compression of dry powder.
Explain process of roller compaction?
Powder is compressed into sheets then gets broken down into smaller particles by a miller. This is repeated for particles that are still too big. If small enough doesn’t go back into the machine to repeat the process.
What is the rumpf classification of intragranular bonding?
1) Attractive forces between particles
2) Attractive forces between immobile films
3) Liquid bridges
4) Solid bridges
5) Mechanical interlocking
What are Attractive forces between particles?
Van der Waals forces between all particles and electrostatic interactions between charged particles.
What are Attractive forces between immobile films?
When particles stick together due to adsorption of moisture on particle surface
What are liquid bridges?
Capillary forces (e.g. surface tension) due to liquid around particles (wet granulation). Stronger force with viscous substances.
What are solid bridges?
Dry granulation: solid binder sintering - compression causes heat to build up partially melting the solids causing them to fuse and when they solidify, they remain fused.
Wet granulation: recrystallization of liquid binder.
What is mechanical interlocking?
Shape-related bonding- rough, angular particles interlock with each other.
