Week 6 - Granulation, Extrusion and Sphereunisation

Question 1

What is the difference between powder, granules and pellets

Answer 1

Powder - very fine particles

Granules - are solid, dry aggregates of powder particles
(i.e. powder agglomerates, large coarse particles)
- sufficient enough to withstand pressure (don’t break)
- do NOT have to be round (like pellets)
- help avoid segregation
- as particles stick together + held in place
- improve flow, mixing and wettability
- contain 1 or more API (with or without excipients)
- used for oral formulations, some swallowed, chewed, dissolved etc.

Pellets - dense, spherical agglomerates
- used for multi-dose + MR
- less porous
- small = pass stomach quicker than tablets (don’t have to dissolve)
- contain 1 or more API and excipients
- can be coated (each individual pellet)
- have ↓ risk of dose dumping compared to granules
- have better flow properties + less friability

Question 2

List the types of interactions between particles

Answer 2

Weak Interactions
- broken easily
- occur due to adhesion / cohesion via liquid films
- occur via electrostatic interactions

Strong Interaction
- Liquid Bridges: (wet granulation)
- formed when solvent + binder is added as particles become more cohesive
- when dries, liquid is removed = fall apart as bridges break
- Solid Bridges: keep particle together
- dry granulation: achieved by melting, pressing molecules tightly together
- wet granulation: achieved by drying of binders
- liquid bridges when solvent + binder present, when dry the solvent is removed and binder is left

Question 3

List the ways granules can be generated (wet and dry granulation)

Answer 3

Granules prepared from powder particles
1. Mixing
2. Aggregation
3. Drying (wet granulation ONLY)
4. Screening (separate powder that hasn’t glue properly as it wont withstand pressure + removes large particles)

1. Dry Granulation
   - compaction, constructive process
   - has a milling step (making particle size smaller)
2. Wet Granulation
   - add a pure solvent (water, ethanol), destructive process
   - form liquid bridges (when solvent added)
   - has drying step (recrystallisation occurs + binders form solid bridges when solvent removed)
   - crystal size depends on drying rate (dry quick = small crystals)

Question 4

How does aggregation with granules occur

Answer 4

• Add solvent or binder
  - binder = excipient that keeps tablet together
  - solubility of granule depends on solubility of binder used
  - agglutinated granules formed when use a binder in a solvent
• aggregation can be constrictive (dry granulation) or destructive (wet)

Question 5

How does Wet Granulation generate granules

Answer 5

Many require drying step

1. Destructive Granulation (HIGH SHEER MIXER)
   
   • mixer blades, move particles over each other
     - shear introduces energy into bulk = temp. ↑ = solvent evaporate
   • press particles through sieve onto trays (destructive as it cuts it into smaller granules)
2. Constructive Granulation (FLUID BED)
   
   • hot air flows from bottom through centre of pipe then falls down on the outside
   • hot air causes solvent to evaporate + dries the binder = solid bridges formed
3. Spray dryers
   
   • solvent is sprayed onto particles
   • as particles fall down they dry = solid bridges formed

Question 6

How does Dry Granulation generate granules

Answer 6

Used if can’t do wet granulation, not used to formulate drug for patient

Push particles strongly together = particles flow around each other
Granules are denser than wet granulation
All require milling step

1. Roller Compaction
   
   • powder flows through a powder feed
   • have 2 rollers which generate flat compaction (sheets)
   • sheets have to be milled (to generate granule size)
2. Slugging
   
   • powder flows through powder feed
   • have 2 rollers which compress powder into a pre-formed shape (slug like shape)

Question 7

What is extrusion

Answer 7

Oressing powder mixture through a tube to generate longer particles (cylinders)

• Used to produce granules, pellets and implants
  - implants administered sub-cutaneously by implant
  - implants are bio-degradable

Extrusion Instruments:
- Screw-feed extruder
- Roll extruder (2 rollers but one is perforated + extrudes into centre)
- Basket extruder

Question 8

List the ways pellets can be generated

Answer 8

1. Extrusion (make long particles)
2. Spheronisation (actual production of peels)

Question 9

What instruments generate pellets

Answer 9

1. Spheronisation
   - cylinders produced (from extrusion) are spun on rotating friction plate + broken into small particles
   - edges of particles softens + round off
   - centre gets pinched, elongation occurs = sphere is formed
   - OR particle elongates, twists around each other + breaks forming 2 spheres (pellets)
   - as plate revolves we add material
   - material gets thrown agains wall but pulled back to centre
   - quick process (<10 min)
   - of spheronise longer = harder pellets
2. Fluid bed dryer
   - air flow from bottom
   - powder is added to rotating plate + binder added
   - pellets form and dry due to warm air
3. Spray drying
   - spray solvent ont particles
   - doesn’t produce many pellets
   - too wet pellets stick together