Pelletization

Question 1

What are pellets?

Answer 1

Small, hard, spherical mass of substance(s)

Question 2

Why are pellets round?

Answer 2

to minimize energy & friction during motion

Question 3

What are the therapeutic advantages of spheroids as a multi-unit dosage form?

Answer 3

1. Minimises local irritation
   (drug release over a wider area)
2. Maximises absorption/ bioavailability
3. ↓ dose dumping effect
   (DD= ↑amt of drug released quickly from CR drug ∵ coat failure of tab)
4. ↑ GER (X blocked by pyloric sphincter)

Question 4

What are the technological advantages of spheronization?

Answer 4

1. Easier to coat
2. Uniformity in packing
3. Spherical shape (min energy)
4. Good flow
5. ↓ friability

Question 5

List the 4 types of pelletization techniques

Answer 5

Direct pelletization

Pelletization via extrusion

Pelletization by layering onto starter seeds

Pelletization through droplet formation

Question 6

What different types of direct pelletization are there? Explain briefly how each method works

Answer 6

1) Fluid bed layering (similar to coating):
coating medium containing solution/ suspension of core material (e.g. metformin solution) is coated successively onto seed particles

2) Balling:
liquid sprayed while rotating powder (disc/ rotary drum pelletizer)
⇒ spherical pellets formed to ↓ friction
⇒ pellets sieved in diff size ranges & balled separately to obtain uniform size

3) ‘One pot’ pelletization: (rotary processor)
agglomeration media sprayed directly onto powder mass rotating in spheroniser on frictional base

Question 7

What are the potential issues of balling/ one pot pelletization?

Answer 7

wide size distribution; not suitable for drug-loaded pellets (varying drug distr)

Question 8

What is the method of choice for pelletization?

Answer 8

Extrusion-Spheronization

Question 9

Why is extrusion-spheronization often used?

Answer 9

• easy to operate
• ↑throughput, ↓wastage
• very efficient

Particles formed:

• highly spherical
• narrow size distribution
• smooth surface
• low friability

Question 10

What are the steps in extrusion-spheronization?

Answer 10

① Dry blending (mix well for uniform composition)
② Wet massing (agglomeration/ granulation)
③ Extrusion (pass through orifice to form long extrudates)
④ Spheronization
⑤ Drying
⑥ Coating

Question 11

What occurs during extrusion?

Answer 11

Moistened powder mixture introduced and processed in extruder to form high density, cylinder-shaped extrudates – pass through screen of desired aperture size

Question 12

What are the features of ideal extrudates

Answer 12

Jagged with regular spaced shark-skinned protuberances (act as break pts to form uniform fragments)

Question 13

What occurs during spheronization?

Answer 13

1. Long extrudates broken into uniform lengths
2. Rounded via rope-like motion in spheroniser with rotating frictional plates
   ⇒ Highly spherical, narrow size distribution (similar size to aperture of extruder screen)

↑ spheronisation time，↓ size distribution

Question 14

What are the formulation requirements for extrusion-spheronisation?

Answer 14

Extrusion:
- Cohesive, plastic wet mass with inherent fluidity and self-lubricating properties
(plasticity ⇒ ✓ deform; self-lubricating ⇒ can flow w/o fragmenting)

Spheronisation:
- Extrudates with sufficient plasticity

Basic formulation:

• Pelletisation aid (prevents disintegration)
• Drug
• filler
• Moistening liquid

Question 15

What is the most commonly used pelletization aid?

Answer 15

Microcrystalline Cellulose (MCC)

Question 16

Why is MCC an ideal pelletization aid?

Answer 16

Good binding property
Good cohesiveness
Large SA
High internal porosity

Question 17

How does MCC act as a pelletization aid?

Answer 17

MCC absorbs water like a molecular sponge

Extrusion:

• gives cohesive yet plastic wet mass
• helps in binding & lubrication

Spheronization:
- ↑ surface plasticity (allows deformation & rounding into spherical pellets)

Question 18

How does quality of extrudates impact the quality of pellets?

Answer 18

Well-formed extrudates ⇒ break into short lengths & rounds quickly

Poorly-formed ⇒ small fragments; pellets build up slowly

Question 19

Why are smaller particles favoured in spheronisation?

Answer 19

Allow production of agglomerates that are more spherical, smoother & ↓size distribution

• *Ideal size of component particles = 1/6 or 1/8 of pellet size
• • large particles ⇒ bumpy surface, wide size distribution

Question 20

How do you estimate the optimal amount of liquid used for spheronisation?

Answer 20

Add liquid to powder mass in mixer bowl of mixer torque rheometer (MTR)
⇒ obtain rheological profile of moistened powder mass

Liquid requirement = W Tmax

Question 21

What are the key factors to ensure spheronization is successful?

Answer 21

• components used must be compatible w/ pelletization aid ⇒ cohesive matrix, good plasticity & lubrication from wetting
• components pack well
• optimal balance of forces to promote rounding

Question 22

How does size of component particles affect strength of pellets?

Answer 22

Coarse: poor packing; ↑ friability

Fine: req more effort due to air entrapment but strong pellets

Wide size distribution: small particles can fit btw large particles ⇒ well packed; strong pellets

Question 23

What kind of binders should be avoided in pelletization? Explain why

Answer 23

Binders w/ migratable stickiness (e.g. PVP, HPMC, melt)

- binder migrates/ follows fluid through powder ⇒ pellet continues to grow (difficult to control size)

Question 24

Give examples of immobile adhesive particles.

Answer 24

micronized particles, MCC

insoluble; X migrate w/ liquid