Pelletization Flashcards
(24 cards)
What are pellets?
Small, hard, spherical mass of substance(s)
Why are pellets round?
to minimize energy & friction during motion
What are the therapeutic advantages of spheroids as a multi-unit dosage form?
- Minimises local irritation
(drug release over a wider area) - Maximises absorption/ bioavailability
- ↓ dose dumping effect
(DD= ↑amt of drug released quickly from CR drug ∵ coat failure of tab) - ↑ GER (X blocked by pyloric sphincter)
What are the technological advantages of spheronization?
- Easier to coat
- Uniformity in packing
- Spherical shape (min energy)
- Good flow
- ↓ friability
List the 4 types of pelletization techniques
Direct pelletization
Pelletization via extrusion
Pelletization by layering onto starter seeds
Pelletization through droplet formation
What different types of direct pelletization are there? Explain briefly how each method works
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
What are the potential issues of balling/ one pot pelletization?
wide size distribution; not suitable for drug-loaded pellets (varying drug distr)
What is the method of choice for pelletization?
Extrusion-Spheronization
Why is extrusion-spheronization often used?
- easy to operate
- ↑throughput, ↓wastage
- very efficient
Particles formed:
- highly spherical
- narrow size distribution
- smooth surface
- low friability
What are the steps in extrusion-spheronization?
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
What occurs during extrusion?
Moistened powder mixture introduced and processed in extruder to form high density, cylinder-shaped extrudates – pass through screen of desired aperture size
What are the features of ideal extrudates
Jagged with regular spaced shark-skinned protuberances (act as break pts to form uniform fragments)
What occurs during spheronization?
- Long extrudates broken into uniform lengths
- 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
What are the formulation requirements for extrusion-spheronisation?
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
What is the most commonly used pelletization aid?
Microcrystalline Cellulose (MCC)
Why is MCC an ideal pelletization aid?
Good binding property
Good cohesiveness
Large SA
High internal porosity
How does MCC act as a pelletization aid?
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)
How does quality of extrudates impact the quality of pellets?
Well-formed extrudates ⇒ break into short lengths & rounds quickly
Poorly-formed ⇒ small fragments; pellets build up slowly
Why are smaller particles favoured in spheronisation?
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
How do you estimate the optimal amount of liquid used for spheronisation?
Add liquid to powder mass in mixer bowl of mixer torque rheometer (MTR)
⇒ obtain rheological profile of moistened powder mass
Liquid requirement = W Tmax
What are the key factors to ensure spheronization is successful?
- 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
How does size of component particles affect strength of pellets?
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
What kind of binders should be avoided in pelletization? Explain why
Binders w/ migratable stickiness (e.g. PVP, HPMC, melt)
- binder migrates/ follows fluid through powder ⇒ pellet continues to grow (difficult to control size)
Give examples of immobile adhesive particles.
micronized particles, MCC
insoluble; X migrate w/ liquid
