CHAPTER 6: SIZE SEPARATION
1. INTRODUCTION
In the pharmaceutical industry, controlling particle size and size range is very
important. Size reduction machines do not always produce particles of uniform or
desired size. Therefore, powders often need to be classified into different grades.
Among various methods available, sieving is the most commonly used technique for
grading powders.
2. SIEVING / SIFTING
Sieving or sifting is the process of separating different grades of powders using
sieves.
Important Terms:
● Tailing: The material that does not pass through the sieve after grinding. It
should never be rejected because it may contain medicinally active
constituents. Instead, it should be added to the next batch for regrinding.
Sieve Construction:
● Sieves consist of a circular frame (wood or metal)
● Fitted with wire-cloth made of copper alloys, stainless steel, hair, silk, nylon, or
terylene
Sieve Numbering:
● The sieve number indicates the number of meshes in 2.54 cm (1 inch) length
● Important: The number indicates meshes, NOT wires
● Example: No. 10 sieve has 10 meshes in 2.54 cm
● Effective sifting area of a No. 10 sieve is only 44% (because wires occupy
space)
3. PHARMACOPOEIAL GRADING OF POWDERS
Pharmacopoeia specifies five grades of powders:
Grade Sieve Specification Description
Coarse Powder 10/44 All particles pass through
No. 10, not more than 40%
pass through No. 44
Moderately Coarse Powder 22/60 All particles pass through
No. 22, not more than 40%
pass through No. 60
Moderately Fine Powder 44/85 All particles pass through
No. 44, not more than 40%
pass through No. 85
Fine Powder 85 All particles pass through
No. 85
Very Fine Powder 120 All particles pass through
No. 120
Why two sieves for the first three grades?
● First three grades have both upper and lower limits (e.g., 10/44)
● This ensures the powder is not too coarse (must pass through upper sieve)
and not too fine (not more than 40% pass through finer sieve)
● Finer grades (85 and 120) have only upper limit because it is easier to obtain
fine powder by continuous grinding
4. IMPORTANCE OF PARTICLE SIZE IN PHARMACEUTICALS
For Extraction:
● Water: Penetrates easily into vegetable tissues → coarser powder can be
used
● Alcohol (60%): Hardens vegetable tissues → slower penetration → finer
powder required
● Soft tissues → coarse powder; Hard drugs → finer powder
For Dosage Forms:
Dosage Form Particle Size Required Reason
Ophthalmic preparations Very fine Avoid irritation from gritty
particles
Ointments, creams, pastes Very fine Avoid irritation
Dusting powders Very fine Smooth application
Oral suspensions, powders, Fine Faster absorption (smaller
tablets, capsules particles = faster
absorption)
Sustained release Large particles Slower absorption →
formulations prolonged action
5. PARTICLE SIZE ANALYSIS METHODS
Two methods are commonly used:
1. Sieving Method
2. Sedimentation Method
5.1 Sampling Precautions (Before ANY Analysis):
● Sample must represent the whole product
● Do NOT take from the top (separation may have occurred during transport)
● Preliminary mixing of container contents is essential
● For multiple containers, use statistical methods for sampling
5.2 SIEVING METHOD
Principle:
● Powder is passed over a shaken perforated screen
● Smaller particles pass through; oversize particles are retained
Procedure for Size Distribution Analysis:
1. Sieves of different sizes are arranged in a tier (stack)
2. Coarsest sieve at the top, followed by increasing mesh numbers downward
3. Powder placed in top sieve
4. Sieves shaken mechanically with gyratory (rotary) and vibratory movements
5. Time and force of vibration are predetermined
6. After shaking, weight of each fraction is determined and percentage
calculated
Difficulties/Errors in Sieving:
Error Cause
Overloading Too much powder on sieves
Insufficient shaking time Incomplete separation
Electrostatic attraction Particles form aggregates
Humidity Hygroscopic powders form aggregates
Particle shape Spherical pass easily; fibrous/plate-like
particles get stuck
Presentation of Results:
● Presented as cumulative oversize curve or histogram
● Semi-log graph paper is used:
○ Particle size on logarithmic scale
○ Proportion passing on arithmetic scale
5.3 SEDIMENTATION METHOD
Principle:
Based on the rate at which particles settle in a liquid medium.
Stoke's Equation:
de = √(18η / (ρ - ρ₀)g × x/t)
Symbol Meaning
de Stoke's diameter (effective diameter)
η Viscosity of dispersion liquid (poises)
x/t Rate of sedimentation (distance/time)
g Gravitational constant
ρ Density of particles
ρ₀ Density of medium
Limitation: Applies only to dilute dispersions with solid concentration ≤ 2% (w/w)
5.4 ANDREASEN METHOD (Pipette Method)
Apparatus:
● Sedimentation vessel (500 ml capacity)
● Fitted with ground glass joint
● 10 ml pipette with two-way stopcock
Procedure:
1. Prepare 1% suspension of powder in suitable liquid
2. Place in sedimentation vessel
3. Withdraw 10 ml samples at specified time intervals from a specific depth
below surface
4. Dry samples and weigh residues
Principle:
● Larger particles settle faster than smaller ones
● They fall below the pipette tip sooner
● Each successive sample contains smaller particles and has lower
concentration
Calculation:
● Percentage of initial concentration is calculated for particles of different sizes
6. CYCLONE SEPARATOR
Construction:
● Cylindrical vessel with a conical base
● Tangential inlet at the top
● Fluid outlet at the top
● Solids outlet at the base
Working:
1. Suspension introduced tangentially at high speed
2. Creates rotary movement inside
3. Fluid exits through top outlet
4. Centrifugal force throws solids to the walls
5. Solids fall to conical base
6. Removed through solids outlet
Uses:
● Primarily used for solid-gas suspensions (air)
● Can also be used for solid-liquid suspensions
● Uses centrifugal force (NOT gravitational force)
Variable Separation:
● Depending on fluid velocity:
○ All particles can be separated
○ OR only coarse particles removed, fine particles carried with fluid
7. COMPARISON TABLE: KEY METHODS
Feature Sieving Method Sedimentation Cyclone
Method Separator
Principle Mesh size Rate of settling Centrifugal force
separation
Force Used Mechanical Gravity Centrifugal
shaking
Medium Dry powder Liquid dispersion Gas (usually) or
liquid
Particle Size Larger particles Can measure down Variable
Range to 0.5 μm
Advantages Simple, rapid, Can measure very Continuous
inexpensive fine particles operation
Limitations Errors due to Only for dilute Efficiency depends
shape, humidity, dispersions on velocity
static
8. KEY POINTS TO REMEMBER (QUICK REVISION)
Point Detail
Tailing Contains active constituents → Do NOT
reject
Sieve number = meshes (not wires) in No. 10 = 10 meshes
2.54 cm
No. 10 sieve Only 44% effective sifting area
Smaller particles Faster absorption
Larger particles Sustained action
Alcohol extraction Needs finer powder
Water extraction Can use coarser powder
Ophthalmic preparations Must use very fine powder
Stoke's equation Only for ≤2% dispersions
Andreasen apparatus Uses 500 ml vessel, 10 ml pipette, 1%
suspension
Cyclone separator Uses centrifugal force (not gravity)
9. IMPORTANT FORMULA
Stoke's Equation:
de = √(18η / (ρ - ρ₀)g × x/t)
Where:
● de = Stoke's (effective) diameter
● η = Viscosity of liquid (poises)
● x/t = Rate of sedimentation
● g = Gravitational constant
● ρ = Density of particles
● ρ₀ = Density of medium
10. CONCLUSION
Particle size control is fundamental in pharmacy because it affects:
● Extraction efficiency of active constituents
● Absorption rate and bioavailability of drugs
● Therapeutic action (immediate vs sustained)
● Patient safety (avoiding irritation from gritty particles)
● Formulation quality of various dosage forms
Sieving remains the most common method for grading powders due to its simplicity,
while sedimentation methods (like Andreasen) are used for finer particles. Cyclone
separators provide continuous separation using centrifugal force.