Since particle size can affect micromeritics of specimen substance,,,, like 1- “Processability ” of powder 2- Final formulation Why measure particle size of pharmaceuticals???
Methods for Determining Particle Size 1-Microscopy 2-Sieving 3-Sedimentation
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
PROCEDURE:
Cont’d
Relatively inexpensive Each particle individually examined Detect aggregates Permanent record – photograph Small sample sizes required For submicron particles, Electron microscopy can be performed. Advantages
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
Sieve A nalysis 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 .
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 )
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.
Easy to perform Wide size range Inexpensive ADVANTAGES
Known problems of reproducibility Wear/damage in use or cleaning Irregular/agglomerated particles Rod-like particles : overestimate of under-size Labour intensive DISADVANTAGES
It is based upon WEIGHT DISTRIBUTION. Sedimentation Techniques These methods depend on the fact that the terminal velocity of a particle in a fluid increases with size. It follows Stoke’s Law.
Stoke’s law Mathematically, Stoke’s Law states that;
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
Pipette method
Equipment required can be relatively simple. Inexpensive Can measure a wide range of sizes with accuracy and reproducibility . ADVANTAGES
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