Granules and Granulation

Question 1

Powders

Answer 1

Usually a mixture of fine powders, including active ingredient, colours, flavours and sweetening agents

Question 2

Granules

Answer 2

• Comprise powder particles that have been aggregated to from large particles sufficiently robust to withstand handling

Question 3

Examples of pharmacutical powder

Answer 3

• Amoxicillin
• Ciplofloxin
• Laxative sachets

Question 4

Pharmaceutical granules

Answer 4

• Colchicine to treat gout
• Cholecalciferol (Vit D3) for osteoporosis
• Pyronaridine as antimalarial

Question 5

Granulation

Answer 5

• Dry primary powders are processed to adhere to larger multi particulate entities

Question 6

Small granules

Answer 6

• 0.2 to 0.4 mm
• Usually used as intermediates to be
  mixed with other excipients prior to
  tablet compaction or capsule filling

Question 7

Large granules

Answer 7

• Often dosage forms in their own right
• 1 to 4 mm

Question 8

Reasons for granulation of powders

Answer 8

• Loosely packed
• Poor flowability
• Not uniform
• Dusty

Question 9

Reasons for granulation of granules

Answer 9

• Denser
• Good flowability
• Uniform
• Reduce dust

Question 10

Reasons for granulation

Answer 10

• Prevention of the segregation of constituents of a powder mix
• Improve flow of properties in powder mix
• Improve compaction of powders and uniformity of mix
• decrease toxic dust
• Decrease caking and increase bulk density less storage space

Question 11

Prevention of segregation after sieving powder

Answer 11

• Small dense particles
  to the bottom and large less dense particles to the top

Question 12

Prevention of segregation after sieving of granules

Answer 12

Granules prevent
segregation of the
constituents of a
powder mix

Question 13

Sifting segregation

Answer 13

• Up and down motion to segregate into a container

Question 14

Trajectory segregation

Answer 14

• Side to side motion in a screw conveyor

Question 15

Fluidisation segregation

Answer 15

• Up and down motion seperating course particles and fluidised fine layers

Question 16

Angle of repose segregation

Answer 16

• Stone pile where granules fall to either side

Question 17

Flowability angle of repose

Answer 17

• Angle of repose
• 25-35 degrees good to excellent
• 36-45 degrees fair to passable
• 45-65 degrees poor to very poor
• > 66 degrees very very poor

Question 18

Tapped density (Df)

Answer 18

Weight of sample/volume of powder after tapping until fully settled

Question 19

Bulk density (Do)

Answer 19

Weight of sample/Volume of powder when poured into cylinder

Question 20

Carr’s index

Answer 20

• Df - Do / Df x 100
• Measures strength and stability
• <10 excellent flow property
• > 38 very very poor

Question 21

Hausner ratio

Answer 21

• Do/Df
• Measure of interparticulate friction
• 1.00-1.11is excellent flow property
• > 1.60 very very poor

Question 22

Wet granulation step 1

Answer 22

• Blend powder solid drug with excipients

Question 23

Wet granulation step 2

Answer 23

• Binder (solvent water and ethanol)
• Adhesion and cohesion forces formed due to liquid bridges formed
• Formation of blackberry structure from vander waals and electrostatic forces mechanicaly interlocking

Question 24

Sugars and natural binder examples

Answer 24

• Sucrose
• Liquid glucose
• Starch paste
• Cellulose
• Alginic acid
• Gelatin

Question 25

Synthetic/semi-synthetic polymers

Answer 25

- Methyl cellulose - Ethyl cellulose - Hydroxypropyl methylcellulose - Hydroxypropyl cellulose - Polyvinal alcohol

Question 26

Wet granulation step 3

Answer 26

- The moist mass is pressed through a sieve to size granules - Mass too moist string forms - If mass too dry the granules will fall appart - Screw feed extruder - axial and radial - Gravity feed extruder - Cylinder/Gear

Question 27

Wet granulation step 4

Answer 27

- Primary granules held together by solid bridges hardening binding agent - Bridges of crystalised drug or excipient from patiral melting/recrystalisation

Question 28

Wet granulation step 5

Answer 28

- Dried granules are passed through sieve shaker

Question 29

Limitations of wet granulation: Cost

Answer 29

- Granulation is an expensive process because of labour, time, equipment, energy and space requirements

Question 30

Limitations of wet granulation: stability and loss of material

Answer 30

- Moisture-sensitive or thermolabile drugs, as well as those exhibiting polymorphisms - Loosing materials during stages of process

Question 31

Limitations of wet granulation: Multiple processing step

Answer 31

- Complexity and make validation and control difficult

Question 32

# - High-shear granulation equipment

Answer 32

- Shear and compaction force exerted by the impeller causes Mixing, densification and agglomeration achieved through

Question 33

Equipment for fluid-bed granulation

Answer 33

- Spraying a binder solution onto a fluidized powder bed

Question 34

Extrusion-spheronization

Answer 34

- Extrudate strands feed rolls cause breakdown into cylinderical pellets

Question 35

Spray-drying granulation

Answer 35

- Use liquid feed into atomiser add drying gas into drying chamber - Dry particles collected

Question 36

Dry granulation Step 1

Answer 36

- Add dry powder which contains drug and excipients

Question 37

Dry granulation step 2

Answer 37

- Compression of dry powder using roller compaction - Powder mix is squeezed between two rollers forming flakes

Question 38

Dry granulation step 3

Answer 38

- Slugging to prepare large tablets that are 25mm in diameter and 10-15mm thick - The slug tablets from compression machine is placed on the oscillatting granulator (milling machine)

Question 39

Dry granulation step 4

Answer 39

- Granules are passed through sieve shaker to form sized granules

Question 40

Limitations of dry granulation

Answer 40

- High force/pressure involved in compaction - More likely to generate dust and cause environmental contamination