Powders and Granulation

Define a pharmaceutical powder.

A dosage form in which a drug is mixed with powdered excipients to produce a homogeneous formulation (final product).

Define a granule.

granules (when used as a dosage form) consist of

powder particles that have been aggregated to form

a larger particle

What is the key structural difference between powders and granules?

Powders consist of individual particles, whereas granules are aggregated clusters of particles.

Differentiate powders for internal and external use.

• Internal: oral powders

• External: dusting powders

What does angle of repose measure?

AND

What is the equation for angle of repose?

Powder flowability.

tan θ = h / r

Interpret angle of repose values.

θ > 50°  ‘unsatisfactory flow

25 < θ < 50       ‘satisfactory flow’

What is bulk density?

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The density of powder, including

interparticle void spaces(air).

What is tapped density?

Density after mechanical tapping reduces void spaces.

Flashcard 12
Q: Define Carr’s Compressibility Index (CCI).

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CCI = [(Tapped density − Poured density) / Tapped density] × 100

Define Hausner’s ratio.

Hausner’s ratio = tapped density / poured density

What does a high Hausner’s ratio indicate?

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picture of summary

Poor powder flow due to high interparticle friction/cohesion.

Why are granulate powders required in pharmaceutical processing? (3)

• Prevent segregation

• Improve flow

• Improve compaction properties

What are the two main granulation methods?

• Wet granulation

• Dry granulation

Describe wet granulation.

•Powders are dry blended and a granulating fluid (normally

 containing an adhesive binder) is added.

What is the role of the granulating fluid in wet granulation?

Forms liquid bridges between particles, promoting aggregation.

Describe dry granulation.

Powders are compressed into slugs, then milled and sieved into granules.

When is dry granulation preferred?

For drugs that are sensitive to moisture or heat.

Explain adhesive and cohesive forces in granulation.

• Adhesive: attraction between different materials

• Cohesive: attraction between similar particles

List the five bonding mechanisms in granules.

1. Adhesive/cohesive forces in immobile liquid film

2. Interfacial forces in mobile liquid film

3. Solid bridges

4. Attractive forces between solid particles

5. Mechanical interlocking

How are solid bridges formed in granules?(3)

Through solvent evaporation, crystallisation, or binder hardening.

What attractive forces act in dry granulation?

In the absence of a granulating fluid, two attractive forces operate:

• Electrostatic forces

• Van der Waals forces

What is mechanical interlocking?

Physical interlocking of particles based on shape and size.

What is a high-speed mixer/granulator? (3)

• powders are mixed in a bowl by the impeller

• granulating fluid is added via a port,

• The chopper is switched on once the moist mass

is formed to break up the mass into granules.

Describe a fluidised-bed granulator.

Heated air fluidises powder while granulating fluid is sprayed, forming and drying granules.

Define pellets.

Small, spherical multiparticulate dosage forms (0.7–2.0 mm).

What are key physical properties of pellets? (4)

• Spherical shape gives good flow

• Narrow size distribution

• Low friability

• High surface area/volume ratio

Why do pellets have high surface area-to-volume ratio?

Due to small radius, increasing dissolution and coating efficiency.

State the surface area-to-volume relationship for spheres.

SA:V ratio = 3 / r

What are the advantages of pellets in the GI tract? (4)

• Uniform distribution

• Reduced irregular dosing

• Reduced ulcer risk

• No dose dumping

What formulation advantages do pellets offer? (3)

• Multiple APIs possible

• Different release profiles—immediate release or controlled release possible,

• Reduced incompatibility issues —incompatible actives can be manufactured

        as separate pellets

What processing advantages do pellets have? (6)

increased bulk density,

-

  -  improved flow properties,

  -  reduced dust production (low friability),

  -  increased strength,

  -  smooth surface (for coating)

  -  regular shape for packing (capsules, tablets)

Disadvantages of pellets in processing?

manufacture is more labour/energy intensive

   than other granulation methods mainly due to

   the high levels of solvent (water) required.

List stages of extrusion–spheronisation.

Dry blending → Wet granulation → extrusion → spheronisation → drying → coating

What happens during extrusion?

Wet mass forms rod-shaped particles of uniform diameter

What happens during spheronisation?

rod-shaped particles are converted into spherical particles via frictional forces.

What happens if water content is too low in granulation? (2)

• Dust formation

• Poor pellet yield

What happens if water content is too high in granulation? (2)

• Over-wetting

• Agglomeration into large spheres

How does extruder type affect pellet quality?

Influences density, shear stress, and temperature.

What is “shark-skinning”?

Surface roughness defect on extrudates.

What factors influence extrudate properties? (3)

• Extrusion speed—•surface ‘roughness’ and ‘shark-skinning’

        may (or may not!) become more

        pronounced with increased speeds

• Temperature—•increased temperatures causes evaporation of granulation fluid

• Screen size/thickness—•diameter of perforations effects pellet size,

    —  screen thickness effects densification of mass

How does spheronisation speed affect pellets?

Influences size, hardness, porosity, and shape.

What is the effect of spheronisation time?

No clear correlation, typically 2–10 minutes.

Why should spheroniser loading be controlled?

Overloading reduces process efficiency and uniformity.

Why is wet mass composition critical?

Determines granulation behaviour and pellet quality.