MICROMETICS:

Definition Science and technology of small particles

Importance Clinically: Particle size affects drug release à pharmacological response

(griseofulvin +)
(nitrofurantoin -)

Physical stability (suspensions)

Manufacturing: Particle size affects

• flow properties
•Volumetric filling
• mixing

Why collect - Shape and surface area of individual particles.

particles of - Size range and number / weight of particles present → total surface area
more than one
size
How to - Size of sphere – diameter
determine - Asymmetrical particle - no unique diameter for the particle
particle size - Equivalent sphere diameter → hypothetical sphere → represents an approximation of
true size and shape of the particle

Different - Sieve diameter - The width of the minimum square aperture through which the particle
types of will pass.
diameters: - Ferrets diameter - The mean value of the distance between pairs of parallel None
tangents to the projected outline of the particle. This can be considered as the
boundary separating equal particle areas.
- Stokes diameter – The free-falling diameter (df, see above) of a particle in the laminar
flow region (Rep < 0.2)
- Martins diameter - The mean chord length of the projected outline of the particle
- Drag diameter - Diameter of a sphere having the same resistance to motion in a fluid as
the particle in a fluid of the same density (r ) and same viscosity (h), and moving at
the same velocity (u) approximates to ds when the particle Reynolds number, Rep, is
small and particle motion is streamlined. i.e. Rep < 0.2)
- Projected area diameter - Diameter of a circle having the same area (A) as the projected
area of the particle resting in a stable position.
Particle size Method chosen depends on:
analysis: • Instruments available
• Limitations of the method
• Properties of the powder

Optical microscopy
Sedimentation
Sieving

Optical • Particle size range:

microscopy – 0.2 µm – 100 µm.
• Emulsion / suspension mounted on a slide, field of sight projected onto a screen.
• Determine:
– Feret diameter,
– Martin diameter,
– Projected area diameter.
• Length and breadth obtained – no depth /thickness (disadvantage).

Sieving • Normally used for grading coarser particles.

• Determine the sieve diameter.
Powder shaken (period of time) à Material is then retained on next finer sieve à Collected
and weighed

• Problems:
– Sieve loading, duration, and intensity of agitation.
Sedimentation

Particle size Sphere

• Minimum surface area per volume.
• Characterize by diameter.

Asymmetric particle:
• Greater surface area per volume.
• Difficult to assign diameter.
• Develop equivalent spherical diameter.

Surface area Adsorption method:

determination • Particles with large specific surface areas = good adsorbents.
methods: • Adsorb either gas or solutes from solution.

Air permeability method:

• Resistance to flow of a fluid (air) through a plug of powder is related to the surface area of
powder.
• Affected by
– Compression
– Irregularity

Particle size Reasons for particle size reduction:

reduction – Mixing.
– Facilitates suspension production.
– Improve dissolution and absorption of drug.

Crack Particles exposed to stress à bond rupture à crack propagation

propagation

Toughness of • Initiation & propagation of crack dependent on the nature of materials:

material • Plastic:
– resist fracture at larger stresses and are tougher in nature
• Brittle:
– crack is easily propagated & cannot withstand high stresses
Changes in
particle size
distribution
curves as size
reduction
occur

Size reduction Cutting methods

methods – Two sets of knives → stationary set & rotating.
– Stationary knives attached to mill casing.
– Rotating knives attached to a central rotor.
– Cut particles as these two come into contact (minimum clearance between two).
– Collect particles at bottom of mill casing.

Compression methods
• Mortar and pestle – not used commonly.
• Compression mills:
– Two cylindrical rolls.
– One driven and other rotated by friction.

Impact method
• Hammers connected to central shaft.
• Hammers swing radially from rotating shaft.

Attrition methods
• Roller mills
• Mounted horizontally.
• Have an adjustable gap b/t.
• Rollers rotate at different speeds.
• Remove sample using a scraper.

Size Separation by sieving

separation
methods Separation by fluid classification:
1. Sedimentation method à
- Particles settle at different rates of velocities with different diameters according to
Stokes diameter.
- Separation dependent on the time of sedimentation.

2. Elutriation method à
Fluid always move in opposite direction to sedimentation.
• If velocity of fluid < settling velocity– particle moves downwards.
• If velocity of fluid > settling velocity– particle moves upwards with liquid.
• Separation dependent on the velocity of the fluid.

3. Cyclone method à
- Outer vortex – high fluid velocity & throws particles to the walls.
- At bottom liquid forms an inner vortex and escapes via the fluid outlet.