pelletisation Flashcards
What are pellets:
Small rounded compressed/tube shaped mass of substance
Advantages of spheronisation:
Therapeutic:
- Minimise local irritation
- Maximise absorption/bioavailability
- Less susceptible to dose dumping
- Reduction in GER
Technological:
- superiority for coating
- uniformity in packaging
- spherical in shape
- good flowability
- low friability
List of pelletisation techniques
Direct pelletisation
Pelletisation through extrusion step
Pelletisation by layering onto starter seeds
Pelletisation through formation of droplets
Direct pelletisation methods:
Fluid bed layering: pelletisation by layering onto starter seeds –> disposition of successive coats onto seed particles without agglomerative growth (coating medium is solution/suspension of core material)
Balling process: involves disc/rotatory drum pelletiser – pellets will not be highly uniform – not for drug loaded ones
Pelletisation in rotatory processor: agglomeration media sprayed directly onto powder mass rotating in spheroniser on frictional base – size distribution of pellets not very tight
Why is extrusion-spheronisation often used:
- Ease of operation
- High throughput, low wastage
- Highly efficient
- Highly spherical
- Pellets of narrow size distribution - no need to sieve particles that are too big/small
- Pellets with smooth surface
- Pellets with low friability
Steps involved in extrusion-spheronisation:
- Dry blending
- Wet blending
- Extrusion
- Spheroisation
- Drying
- Coating
What is involved in the extrusion step:
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, featured with regular spaced shark-skinned protuberances – broken up easily
What is involved in the spheronisation step:
- Cylindrically shaped extrudates broken into uniform lengths and rounded in spheroniser with rotating frictional plate
- Rapid process rounds break extrudates by rope like motion
- Highly spherical, narrow distributed pellets of size close to extruder screen aperture formed
As spheronisation time increases, size distribution decreases
Formulation requirements for extrusion-spheronisation
Extrusion:
- Cohesive, plastic wet mass with inherent fluidity and self-lubricating properties
Spheronisation:
- Extrudates with sufficient plasticity
Basic formulation:
- Pelletisation aid
- Drug
- filler
- Moistening liquid
Most commonly used pelletisation aid:
Microcrystalline cellulose
What are desirable properties of microcrystalline cellulose:
Good binding property
Good cohesiveness
Large surface area
High internal porosity
Molecular sponge model
MCC absorbes water like sponge during extrusion –> cohesive and plastic wet mass –> liquid present helps it stay together and be extruded
Helps in binding and lubrication during spheronisation by increasing surface plasticity and help with rounding extrudates into pellets
Crystallite gel model:
MCC particles broken down into single crystallites of colloidal size – form crystallite gel and immobilise liquid
Plasticity and lubricative properties also increased
Function of MCC in extrusion-spheronisation
Extrusion:
- Form cohesive and plastic wet mass
- Help with binding ad extrusion
Spheronisation:
- increase surface plasticity
- Help round extrudates into pellets
Types of pelletisation aids (dont memorise unless you have brain power)
powdered cellulose
hydroxylpropyl methylcellulose/hypromellose
hydroxyethyl cellulose
chitosan
carrageean
cross-linked polyvinyl pyrrolidone (2nd best after MCC)
How do quality of extrudates impact quality of pellets:
Poorly formed extrudates fragment and build up pellets slowly
Well-formed extrudates break into short lengths and round quickly
Why are smaller particles favoured in spheronisation:
smoother surfaces and narrower size distributions
optimal amount of liquid used in spheronisation:
80-90% Tmax – capillary form
How to get round pellets with narrow distribution:
Cohesive forces close to forces added during spheronisation
if cohesive forces< forces: decrease spheronisation speed repeat extrusion step reduce component particle size Widen component particle size distribution for better packability
if cohesive forces> forces:
Increase spheronisationn speed
factors affecting packability of component particles in pelletisation
depends on particle size and size distribution of components and forces exerted during wet processing
critical in spheroid formation
Factors for successful spheronisation process:
in process particle size and overall matrix cohesiveness during wet processing steps
Ability of components to pack well
Optimal balance of forces and processing conditions that promote rounding
Impt point related to cohesivity and pelletisation (sry i cant think of a better description)
Cohesivity is important for pelletisation but cannot have migratable stickiness cos if binder can migrate with flud, pellet will keep growing and sizes will be variable
use immobile adhesive particles
Types of particles related to type of pellets formed:
Coarse particles – loosely packed friable pellets
Small particles – well packed strong pellets
Wide size distribution of particles – well packed strong pellets
Example of immobile adhesive particles:
micronised powders, MCC
