Pellets & Pelletization

Question 1

Advantages of spheroids as multi-unit dosage form

Answer 1

Therapeutic:

• Minimise local irritation
• Maximise absorption/bioavailability
• Less susceptible to dose dumping
• Reduce GER

Technological:

• Superiority for coating
• Uniformity in packing
• Spherical in shape
• Good flowability
• Low friability

Question 2

What are the Pelletization techniques?

Answer 2

1) Direct pelletization
2) Pelletization through extrusion step
3) Pelletization by layering onto starter seeds
4) Pelletization through formation of droplets

Question 3

What is Fluid Bed Layering

Answer 3

• Pelletization by layering onto starter seeds

- -> Layering: Deposition of successive coats onto the seed particles without agglomerative growth

Question 4

What is the Balling Process used for?

Answer 4

Use: Produce nonpareils as well as agriculture and industrial pellets, industrial pellet production use

Question 5

Eg. of Direct Pelletization

Answer 5

1) Pelletization in Rotary Processor
- a “one-pot” pelletization process
- Conducted by spraying the agglomeration media directly onto the powder mass rotating in a spheronizer on a frictional base
- Pellets formed in situ; can be directly coated by changing spray media to coating media with introduction of drying air

Question 6

What is the method of choice for producing pellets?

Answer 6

Extrusion-spheronization

Question 7

Advantages of Extrusion-spheronization

Answer 7

• Ease of operation
• Efficient, High throughput with low wastage
• Produces highly spherical aggregates
• Pellets have narrow size distribution
• Pellets have smooth surface
• Pellets have low friability

Question 8

Steps in Extrusion-spheronization process

Answer 8

1) Dry blending
2) Wet massing

3) Extrusion (Radial/Axial extruder)
- moistened powder mixture is introduced & processed in the extruder to form high-density, cylinder shaped extrudates
- pass extrudates through screen of desired aperture size

4) Spheronization
- extrudates are broken into uniform length & rounded in a spheronizer with a rotating frictional plate to produce spheroids
- rapid process
- shaping process due to plastic deformation

5) Drying
6) Coating

Question 9

Formulation requirements of extrusion-spheronization

Answer 9

Extrusion:
- Wet mass is cohesive & plastic with inherent fluidity & self-lubricating properties

Spheronization:
- Extrudates have sufficient plasticity

Basic formulation:

• Pelletization aid
• Drug
• Filler
• Moistening liquid

Question 10

What is the Pelletization aid of choice?

Answer 10

Microcrystalline cellulose (MCC)

• Good binding property
• Good cohesiveness
• Large SA
• High internal porosity

–> Gives unparalleled efficiency for preparing highly spherical granules of narrow size distribution with desired mechanical properties

Question 11

Functions of MCC?

Answer 11

• Absorbs H2O like a “molecular sponge” during extrusion
• > Give a cohesive yet plastic wet mass
• > Help in binding & extrusion
• Help in binding & lubrication in spheronization
• -> Increases surface plasticity & helps in rounding extrudates into pellets

Question 12

Examples of Pelletization Aids

Answer 12

• Microcrystalline cellulose, MCC Ideal
• Cross-linked polyvinyl pyrrolidone (very successful)
• Powdered cellulose
• Hydroxyethyl cellulose
• Chitosan
• Carrageenan
• Hydroxypropyl methylcellulose/Hypromellose

Question 13

Small/larger particles favoured for ensuring pellet sphericity?

Answer 13

Ans: Small

• Will form agglomerates that are more spherical, smoother surface, narrow size distribution

Question 14

What is the moisture requirement by mixer torque rheometer (MTR)?

Answer 14

• Peak of the graph
• Moistening liquid added to powder mass in the mixer bowl of the MTR
• Rheological profile of moistened powder mass is obtained

Question 15

What is the strategy for successful pelletization

Answer 15

• Ensuring wet packability*
• Critical for influencing spheroid formation
• Depends on the particle size & size distribution of its components & forces exerted during wet processing

Dry powder —[moistening liquid]—> Wet mass
Wet mass — Extrusion —> Extrudate
Extrudate – Spheronization —> Round spheroids with
narrow size distribution

During spheronization, cohesive forces should be ~ forces to make good extrudates

Question 16

What is crucial for successful spheronization process?

Answer 16

• Ability of components to pack well
• Optimal balance of forces for spheroid formation
• Functionality of spheronization aid is dependent on its process particle size & overall matrix cohesiveness during wet processing steps

Question 17

Why is wide size distribution preferred > small particles?

Answer 17

Though small particles are well packed & will form strong pellets, they trap air & need effort to remove