Oral solid dosage forms

What is the aim of solid dosage form (SDF) design?

To develop dosage forms by understanding material properties and formulation factors,

that influence performance and manufacturability.

Why are APIs rarely administered alone in solid dosage forms?

Due to small dose size, poor processing characteristics, or need for specialised functionality.

Classify powders based on particle size.(4)

• Coarse: >1000 µm

• Intermediate: 100–1000 µm

• Fine: 5–100 µm

• Ultrafine: <5 µm

How does particle shape affect powder flow? (2)

• Spherical: good flow

• Acicular (needle-like): poor flow

How does particle density influence powder behaviour?

• Higher density → heavier, better settling

Lower density → lighter, more prone to segregation

What are common light-based methods for particle size analysis? (4)

• Light microscopy

• SEM/TEM

• Laser diffraction

• Photon correlation spectroscopy

What is the principle of sieving in particle size analysis?

Particles smaller than the sieve aparatus pass through successive meshes, separating into fractions.

Used extensively for blends, granulations etc.

What is the limitation of sieving for API analysis?

Requires large sample volumes, so not suitable for APIs.

How are particle size results typically represented? (2)

• Histograms or frequency curves

• Cumulative distributions (oversize/undersize)

What is meant by “equivalent sphere” in particle sizing?

Representing irregular particles as spheres based on length or volume for measurement.

Why must powder samples be representative?

Powders segregate due to size, shape, and density differences.

Compare dynamic and static sampling.

• Dynamic: •taking a proportion when the product is in motion (best). Take several samples at varying times when the powder is in motion.

• Static: taken at rest (less reliable due to segregation)

Differentiate adhesion and cohesion.

• Adhesion: attraction between different materials

• Cohesion: attraction between similar materials

What determines powder flow behaviour AND SHAPE?

Balance between cohesive and external forces.

Define angle of repose.

The maximum angle between a powder heap and horizontal plane, indicating flowability.

How do particle size and moisture affect angle of repose?

Smaller size and higher moisture → increase angle → poorer flow.

What is bulk density?

Density of a powder including

void spaces (air) between particles/packing fraction (k). .

What does a high bulk density indicate about flow?

Better flow due to reduced porosity.

Percentage of the volume which is taken up by air is known as the bed porosity.

What is Hausner’s ratio and what does it indicate?

Hausner’s ratio = tapped BD / poured BD

• ≈1 → non-cohesive powder with good flow

1.5 → cohesive powder with poor flow

What is Carr’s Compression Index (CCI)?

CCI = [(tapped BD – poured BD) / tapped BD] × 100

• <10 → excellent flow

20 → poor flow

Define powder mixing.

A unit operation that ensures uniform distribution of all components at particle level.

What is segregation in powder systems?

Separation of mixed particles due to differences in size, density, or shape.

Describe three types of segregation.(3)

• Percolation: small particles move downward

• Trajectory: heavier particles travel further

• Elutriation: fine/light particles rise with airflow

What is trituration?

Mixing powders using a mortar and pestle.

Types of mixtures(3)

•. Positive mixture- Diffusion, irreversible – no problems

• Negative mixtures -Density, size or shape differences.

  •Spontaneously separate out (segregate).

• Neutral mixtures- No movement without addition of energy.

What is the scale of scrutiny (SoS)?

The sample size required to determine whether the formulation has been mixed enough,

also equal to the dose unit weight/volume.

How is SoS calculated?

SoS = (dose / %API in blend) × 100

Define comminution?

Reduction of large solid masses into smaller units by mechanical means.

What factors must be considered in particle size reduction?(4)

• Material properties (hardness, structure)

• Desired particle size/shape

• Equipment used

• Energy input and losses

What problems can arise during particle size reduction?
(5)

• Aggregation

• Degradation

• Polymorphic changes

• Moisture changes

• Contamination

What are excipients and their functions in solid dosage forms?(5)

• Help convert API into dosage form

Various specialized functions:

• Aid manufacture

• Improve stability and bioavailability

• Enhance patient compliance

• Provide bulk and identification

what is the use of disintegrants ? (4)

• To promote the break-up of solid unit dosage forms following ingestion.

• Three mechanisms:

-•Facilitation of water uptake

-•Rupture of tablet by swelling

-•Rupture of tablets by CO₂ production