Pellets, Extrusion and Pharmaceutical 3D printing

Properties of pharmaceutical pellets

• dense spherical agglomerates

• 0.5-1.5mm

• Contain multiple drugs and excipients

Why are pharmaceutical pellets used ?

• coated ones are used for modified release

• Used to fill capsules or pressed into tablets

• Can be administered directly

• Possible to manufacture incompatibility ingredients in separate pellets - then incorporated into s single dosage form

• They’re small and pass through the stomach quicker than tablets

What are some advanatages of their quick passage through the stomach ?

• do not need to disintegrate

• Better ability to pass through the pylorus intact

How are pellets and granules different ?

• Pellets are larger

• Pellets are commonly produced from granules - process called extrusion spheronisation

Making pellets

1. Granulation

2. Extrusion - granules made into a rod shape (like squeezing toothpaste)

3. Pelletisation - rough pellets made into cylindrical shape

4. Spheronisation - pellets made spherical

5. Drying

Steps of extrusion

• wet granules formed into agglomerates and then into long rods through an extruded

Steps of spheronisation

Mechanism of Spheronisation

• plastic deformation

• Break up of ‘dumb-bell’

• Incorporation of fines

Difference between spheronised pellets vs crude granules

Spheronised pellets show;

• greater density

• Better flow properties

• Lower friability

• Narrower particle size distribution

• More uniform packing

What does greater uniformity in particle properties lead to ?

1. Greater ease of handling

2. Easier and more uniform coating

3. Lower risk of dose dumping

4. More reproducible and predictable pharmacokinetic profile

5. Less irritation of the gator-intestinal tract

What are some important parameters for extrusion ?

1. Extruded screen design and extrusion speed - influence density and surface roughness of extrudate

2. Extrusion temperature - influence the wetness of the granulation mass

3. Properties of the feed material

Important parameters for spheronisation

• spheronisation speed and mass of load

• Momentum (mass x velocity) determines forces exerted on particles

• Influences hardness, roundness, porosity, bulk and tapped densities, friability, flow properties and surface structure

• Higher momentum generally leads to smaller and denser pellets

What other processes does extrusion influence ?

• 3D printing - raw material (containing drug + excipients ) is laid down layer by layer

Two different types of extrusion

1. Semi-solid extrusion

2. Hot melt extrusion

What type of medicine is extrusion and 3D useful for ?

• personalised medicine - tailored doses, dosage forms with different shapes