3. Since particle size can affect micromeritics of specimen substance,,,, like
1- “Processability” of powder
2-Final formulation
WHY MEASURE PARTICLE SIZE OF
PHARMACEUTICALS???
5. In this method, small sample size is mounted on the stage of microscope and
the particle size is measured using the MICROMETER joined to it…….
MICROSCOPY
Size Range: 0.2 to about 100 Micrometer
6. Firstly, the powdered substance is placed over the stage and obseved
through the lens.
The microscope eyepiece is fitted with a micrometer by which the
size of the particles can be estimated.
The field can be projected onto a screen where the particles are measured
more easily, or a photograph can be taken from which a slide is prepared and
projected on a screen for measurement.
PROCEDURE:
7. CONT’D
The particles are measured along an arbitrarily chosen fixed line, generally made
horizontally across the center of the particle.
Popular measurements are;
Feret diameter -- Martin diameter -- Projected area diameter
These measurements can be stored as screenshot for long term use.
8. Relatively inexpensive
Each particle individually examined
Detect aggregates
Permanent record – photograph
Small sample sizes required
For submicron particles, Electron microscopy can be performed.
ADVANTAGES
9. Time consuming
High operator fatigue
No information about 3D,, just 2D info about specimen particles
In case of electron microscopy, materials such as emulsions
difficult/impossible to prepare.
DISADVANTAGES
10. Sieve Analysis is performed using a nest or stack of sieves where each lower
sieve has a smaller aperture size than that of the sieve above it.
SIEVING
Size Range: 5μm - ~3mm
It is based upon WEIGHT DISTRIBUTION.
11. Sieving may be performed wet or dry, by machine or by hand, for a fixed time
or until powder passes through the sieve at a constant low rate
METHODS
Machines:
– Shaking
– Vibration
– Use a jet of air to clear the sieves
– Ultra-sonics (wet sieving)
12. Mass of sample is placed on the proper sieve in a mechanical shaker.
The powder is shaken for a definite period of time, and the material that passes
through one sieve and is retained on the next finer sieve is collected and weighed.
When a detailed analysis is desired, the sieves can be arranged in a nest of about five
with the coarsest at the top.
PROCEDURE
Assuming a log-normal distribution, one plots the cumulative percent by weight of powder retained on
the sieves on the probability scale against the logarithm of the arithmetic mean size of the openings of
each of two successive screens.
14. Known problems of reproducibility
Wear/damage in use or cleaning
Irregular/agglomerated particles
Rod-like particles : overestimate of under-size
Labour intensive
DISADVANTAGES
15. It is based upon WEIGHT DISTRIBUTION.
SEDIMENTATIONTECHNIQUES
These methods depend on the fact that the
terminal velocity of a particle in a fluid increases
with size.
It follows Stoke’s Law.
18. Allow a homogeneous suspension to settle in a cylinder, take samples from the
settling suspension at a fixed horizontal level at intervals of time.
• Each sample will contain a representative sample of the suspension, with the
exception of particles greater than a critical size, all of which will have settled
below the level of the sampling point.
• The concentration of solid in a sample taken at time t is determined
• This concentration expressed as a percentage of the initial concentration
gives the percentage (w/w) of particles whose falling velocities are equal to or
less than x/t. Substitution in the equation above gives the corresponding
Stokes' diameter.
PROCEDURE
20. Equipment required can be relatively simple.
Inexpensive
Can measure a wide range of sizes with accuracy and reproducibility.
ADVANTAGES
21. Large particles create turbulence, are slowed and are recorded undersize.
Particle re-aggregation during extended measurements.
Particles have to be completely insoluble in the suspending liquid.
DISADVANTAGES