Pellets and Pelletization Flashcards
What is the definition of a pellet, and what is the form conversion of pellets in pharmaceuticals?
small, rounded, compressed mass of a substance.
powder–> spheroids/pellets –> multi-particulate/multi-unit dosage form
What are the advantages of spheroids as multi-unit dosage form?
Therapeutic
- minimise local irritation
- maximise absorption/bioavailability
- less susceptible to dose dumping
- reduction in gastric emptying rates
Technological
- superiority for coating
- uniformity in packing
- spherical in shape
- good flow ability
- low friability
What is the difference, response-time wise, between a prompt and sustaining dose?
- sustaining dose has a significantly higher response than prompt dose.
- sustaining dose takes a longer time to reach maximum level of response than prompt dose.
What are the different pelletization techniques to make/fabricate spheroids?
- Direct pelletization
- Pelletization through extrusion step
- Pelletization by layering onto starter seeds
- Pelletization through formation of droplets
What is direct pelletization and its techniques?
- single-step pelletization method
- fluid bed layering: spray material (e.g. lactose powder) on starter seed so that it gains weight and eventually becomes round.
- balling methods: put particles in mixer, spray liquid in the mixer with time and turn it round continuously, so that spheroids absorb the fluid and become round.
» Limitation: uneven wide size distribution, requires sieving into different size fractions. - pelletization in a rotary processor (“one-pot pelletization process): spin the powder round the cylinder, spray the liquid so that the powder will become pellets.
What are the advantages of extrusion-spheronization?
- ease of operation
- high throughput with low wastage
- very efficient
- highly spherical aggregates
- pellets of narrow size distribution
- pellets with smooth surface
- pellets with low friability
What are the steps of the extrusion-spheronization process?
- dry blending (mix powder well)
- wet massing (add liquid for powder to agglomerate)
- extrusion (force material through the orifice, so that after it passes through the machine, it becomes an exudate).
- spheronization
- drying
- coating
What is the extrusion step?
- moistened powder is passed through a radial or axial extruder and processed to form high-density, cylindrical extrudates.
- screen aperture size that powder is passed through should be similar in size to the desired pellets manufactured.
What is the spheronization step?
- cyllndrically shaped extrudates are broken into uniform lengths.
- then, they are rounded in a spheronizer with a rotating frictional plate to produce spheroids in a “rope-like motion”.
- shaping process is due to deformation.
- entire process takes about 7 minutes.
What is the takeaway from pellet formation by real-time imaging?
- extrudates are flat with large size distribution
- slowly progress to pellets that are round with narrow size distribution upon extrudation.
What are the formulation requirements for extrusion-spheronization?
- Specific requirement for extrusion
» cohesive, plastic wet mass with inherent fluidity and self-lubricating properties - Specific requirement for spheronization
» extrudates with sufficient plasticity
- Basic formulation >> Pelletization aid >> Drug >> Filler >> Moistening liquid
What is the material commonly used to make pelletization aid and why is it the aid of choice?
- Microcrystalline cellulose
Advantages:
- good binding property
- good cohesiveness
- large surface area
- high internal porosity
- gives unparalleled efficiency for preparing highly spherical granules of narrow size distribution and with the desired mechanical properties.
What are the different models for MCC as pelletization aid?
- Molecular sponge model
Extrusion:
» MCC forms a cohesive yet plastic wet mass
» Helps in binding and lubrication during spheronization
Spheronization:
» Increases surface plasticity, and rounds extrudates into pellets. - The crystallite gel model
» MCC particles are broken into single crystallites of colloidal size which are able to form a crystallite gel and immobilise the liquid.
What is another alternative pelletization aid that is very successful?
cross-linked PVP
What are some tips on making good pellets (extrusion-spheronization)?
Check that pellets are:
- well-formed extrudates
- can be broken into short lengths
- round quickly
Ensure pellet sphericity
- smaller particles are favoured for producing agglomerates that are more spherical, with smoother surfaces and of narrower size distributions.
Moisture requirement
- Add moistening liquid to powder mass in the mixer bowl of the mixer torque rheometer.
- obtain rheological profile of moistened powder mass at 80-90% Tmax.
What is the importance of packability of component particles?
- packing influences spheroid formation
- packability depends on the particle size and size distribution of its components, and the forces exerted during wet processing.
What is required for a successful spheronization process?
- functionality of a spheronization aid is dependent on its in-process particle size, and overall matrix cohesiveness during the wet processing steps of extrusion-spheronization
- ability of the components to pack well
- optimal balance of forces, and process conditions promoting rounding.
What happens to coarse particles, small particles, particles with wide size distribution when moistening liquid is added to them?
coarse particles– loosely packed, friable pellets
small particles – well packed, strong pellets
wide size distribution – well-packed, strong pellets
What are some things to take note of regarding cohesivity of the pellets?
- cohesivity is important for pelletization, but
- cannot have migratable stickiness (e.g. use PVP, HPMC or melt)
- and must use immobile adhesive particles (e.g. MCC)
