Pharmaceutics: Granulation

Question 1

What is the BP definition of a granule?

Answer 1

A solid, dry aggregate of powder particles sufficiently resistant to withstand handling. They are intended for oral administration.

Question 2

What are the types of granules?

Answer 2

Effervescent, coated, gastro-resistant, modified release

Question 3

Typical size of granules are?

Answer 3

200um to 4mm

Question 4

What are granules of 200-500um size used for?

Answer 4

Intermediate pharmaceutical products e.g. to become a tablet or capsule

Question 5

What are granules of >500um size used for?

Answer 5

They form a dosage form in their own right.

Question 6

What are the benefits of granules?

Answer 6

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.

Question 7

What are the drawbacks/cons with using granules?

Answer 7

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)

Question 8

What is the aim of the granulation process?

Answer 8

To aggregate particles to form granules. So in essence particle size is enlarged.

Question 9

Three necessities for making granules?

Answer 9

1) Powder ingredients
2) Binding solution/powder
3) Granulator

Question 10

What are the two types of granulations?

Answer 10

Wet and dry

Question 11

What are the four stages of the granulation process?

Answer 11

1) Mixing
2) Aggregation
3) Drying (if it’s wet granulation)
4) Sieving

Question 12

Types of binders used in wet and dry granulation?

Answer 12

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

Question 13

What is a binder?

Answer 13

An inter-particle glue. It sticks the powder particles together for form an aggregate

Question 14

What affects the solubility of a granule?

Answer 14

The type, amount and solubility of the binder used.

Question 15

Explain stage 1 of wet granulation?

Answer 15

1. 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.

Question 16

Explain stage 2 of wet granulation?

Answer 16

2. Consolidation and Coalescence.

Other particles collide with the nuclei and deform and adhere to the nuclei.

Question 17

Important parameters to consider with stage 1 of wet granulation?

Answer 17

• droplet size
• wetting properties (e.g. surface tension of binder)
• particle flux in wetting zone

Question 18

Important parameters to consider with stage 2 of wet granulation?

Answer 18

• particle surface and moisture
• particle hardness (resistance to deformation)
• particle velocity

Question 19

Important parameters to consider with stage 3 of wet granulation?

Answer 19

• particle velocity

- granule porosity

Question 20

Explain stage 3 of wet granulation?

Answer 20

3. Attrition and breakage.#

Fine particles shed from dry granule surface and dry granules break up

Question 21

How does a high-shear mixer granulator work?

Answer 21

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.

Question 22

Problems with using the High-shear mixer-granulator

Answer 22

can elevate temperature which can cause solvent evaporation or formulation instability.

Question 23

How does a Fluidised-bed granulator work?

Answer 23

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

Question 24

Three means of spraying the binder in the fluidised-bed granulator

Answer 24

top, side and bottom sprays

can watch videos linked in lecture

Question 25

Why is dry granulation used?

Answer 25

for substances that can’t be wetted (e.g. due to being heat or moisture sensitive)

Question 26

What are the two stages of dry granulation?

Answer 26

1) powder compaction

2) Milling

Question 27

What does milling do?

Answer 27

Reduce particle size

Question 28

Explain the process of slugging?

Answer 28

Loose tablet are produced by light compression of dry powder.

Question 29

Explain process of roller compaction?

Answer 29

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.

Question 30

What is the rumpf classification of intragranular bonding?

Answer 30

1) Attractive forces between particles
2) Attractive forces between immobile films
3) Liquid bridges
4) Solid bridges
5) Mechanical interlocking

Question 31

What are Attractive forces between particles?

Answer 31

Van der Waals forces between all particles and electrostatic interactions between charged particles.

Question 32

What are Attractive forces between immobile films?

Answer 32

When particles stick together due to adsorption of moisture on particle surface

Question 33

What are liquid bridges?

Answer 33

Capillary forces (e.g. surface tension) due to liquid around particles (wet granulation).
Stronger force with viscous substances.

Question 34

What are solid bridges?

Answer 34

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.

Question 35

What is mechanical interlocking?

Answer 35

Shape-related bonding- rough, angular particles interlock with each other.