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.
