MICROMERITICS

PHYSICAL PHARMACY LECTURE

MICROMERITICS TERMS TO DESCRIBE PARTICLE SIZE

• Science and technology of small particles • Feret diameter

o Particle size is inversely proportional to o 2 tangents of opposite side of particles
surface area, thus bioavailability • Martin diameter
• The unit of particle size used is the micrometer o Length of a line that bisects particle
(μm), micron (μ), and equal to 10-6 m image (cross-sectional)
• Projected Area diameter
IMPORTANCE OF MICROMERITICS o Estimating a circle assuming that’s the
area
1. Particle size plays an important role for dosage ▪ Projected area diameter is the
forms diameter of the circle estimated
2. Physical stability
3. Pharmacologic response
4. Flow / dissolution properties for solid
formulations
(fine particles = less flow, more dissolution)
5. Proper mixing of granules and powders

SIZE AND RANGE OF PARTICLES IN

PHARMACEUTICAL PREPARATIONS

FORMULA

∑𝑛𝑑
𝑑𝑎𝑣𝑒 =
∑𝑛

SIEVING

• RANGE: 40 μm to 9500 μm

METHODS OF DETERMINING PARTICLE • Official method of particle size determination

SIZE o Though only limited range

OPTICAL MICROSCOPY • Stack of sieves is arranged in order, the powder

is placed on the top of the sieve, the stack
• RANGE: 0.2 μm to 100 μm shaken and the quantity of powder resting on
each sieve weighed
• Prasad and Wan used video recording
equipment to observe, record, store, and retrieve • The mesh openings or mesh no. of the sieve
particle size data from microscopic examination refer to the number of square opening per linear
of tablet excipients including microcrystalline inch
cellulose, Na CMC, MC
FORMULA
• The microscope eyepiece is fitted with a
micrometer by which the size of the particles ∑(%𝑟𝑒𝑡𝑎𝑖𝑛𝑒𝑑 × 𝑎𝑣𝑒. 𝑠𝑖𝑧𝑒 𝑜𝑟 𝑚𝑒𝑎𝑛 𝑜𝑝𝑒𝑛𝑖𝑛𝑔)
𝑑𝑎𝑣𝑒 =
may be estimated 100
 ADSORPTION METHOD

• Amount of gas adsorbed

AIR PERMEABILITY TEST

DERIVED PROPERTIES OF POWDERS

• VOLUME
o True Volume
o Granule Volume
o Bulk Volume
*sieve no. 8 for soil
• POROSITY
SEDIMENTATION o Intraparticle Porosity
o Interspace Porosity
• RANGE: 0.08 μm to 300 μm • DENSITY
o True Density
• The particle size in the subsieve range maybe o Granule Density
obtained by gravity sedimentation as expressed ▪ Displacement of Hg
by Stoke’s Law o Bulk Density
o Stoke’s Law exhibit free fall ▪ Inversely with bulkiness
• BULKINESS
Poise = dynes / cm • FLOW PROPERTIES
Dynes = g / cm sec2
POROSITY OR VOIDS (𝜀)
FORMULA
• ratio of the void volume to the bulk volume

18𝜂0 ℎ
𝑑𝑠𝑡 = √ • frequently expressed in percent
(𝜌𝑠 − 𝜌0 ) 𝑔𝑡
• suppose a nonporous powder is placed in a
USING ANDREASEN PIPET graduated cylinder
o the total volume occupied is known as
• It is a special cylindrical container designed such
the bulk volume (Vb)
that a sample can be removed from the lower
portion at selected time intervals FORMULA
o E.g. suspension and emulsion
𝑉𝑏 = 𝑡𝑟𝑢𝑒 𝑣𝑜𝑙𝑢𝑚𝑒 + 𝑣𝑜𝑙𝑢𝑚𝑒 𝑜𝑓 𝑠𝑝𝑎𝑐𝑒𝑠 𝑏𝑡. 𝑝𝑎𝑟𝑡𝑖𝑐𝑙𝑒𝑠
• The powder is dispersed in nonsolvent in the
𝑉𝑏 − 𝑉𝑝 𝑉𝑝
Andreasen Pipet, agitated, and 20 mL. Samples 𝜀= = 1−
removed over a period of time. Each 20 mL 𝑉𝑏 𝑉𝑏
sample dried and weighed

PARTICLE VOLUME MEASUREMENT

• A popular instrument to measure the volume of

particles is the Coulter Counter

• Principle that when a particle is suspended in a

conducting liquid pass through a small orifice, on
either sides of which are electrodes, a change in PACKING ARRANGEMENTS
electric resistance occurs
• Loose packing, increases porosity due to
increase air space
 • Closest packing or rhombohedral or triangle COHESIVENESS
o 26% porosity
▪ Angles of 60o and 120o are • (sticky) to improve flow characteristics, glidants
common are added to granular powders.
o Examples of glidants
• Loosest or most open or cubic open ▪ Magnesium stearate
o 47% porosity ▪ talc
▪ At 90o angles ▪ starch

METHODS OF DETERMINING PARTICLE COMMON MANUFACTURING PROBLEMS

SIZE ARE ATTRIBUTED TO POWDER FLOW

• Powder transfer through large equipment such

TYPES OF DENSITIES
as hopper
• TRUE DENSITY (ρt)
• GRANULE DENSITY (ρg) • Uneven powder flow
• BULK DENSITY (ρb) o lead to entrapped air within powders
▪ capping or lamination
FORMULA • CAPPING: above
• LAMINATION: middle
• Relative volume of the interspaces voids to the
o increase particle’s friction with die wall
Vg of the powder, exclusive of the intraparticle
▪ lubrication problems
pores (granules)
▪ increase dust contamination
𝑉𝑔 − 𝑉𝑝 𝑉𝑝 𝜌𝑔 risks during powder transfer
𝜀𝑖𝑛𝑡𝑟𝑎𝑝𝑎𝑟𝑡𝑖𝑐𝑙𝑒 = =1− =1−
𝑉𝑔 𝑉𝑔 𝜌𝑡
• Non-uniformity (segregation) in blending
• Relative volume of the interspaces voids to the
Vb of the powder, exclusive of the intraparticle • Powder storage
pores (bulk) o E.g. result in caking tendencies within a
vial or bag after shipping or storage time
𝑉𝑏 − 𝑉𝑔 𝑉𝑔 𝜌𝑏
𝜀𝑖𝑛𝑡𝑒𝑟𝑝𝑎𝑟𝑡𝑖𝑐𝑙𝑒 = =1− =1−
𝑉𝑏 𝑉𝑏 𝜌𝑔
CARR’S CONMPRESIBILITY INDEX
• Is made up of voids between the particles as
well as the pores within the particles 𝜌𝑡𝑎𝑝𝑝𝑒𝑑 − 𝜌𝑏𝑢𝑙𝑘
𝐶𝑎𝑟𝑟 ′ 𝑠 𝑖𝑛𝑑𝑒𝑥 (%) = × 100
𝜌𝑡𝑎𝑝𝑝𝑒𝑑
𝑉𝑏 − 𝑉𝑝 𝑉𝑝 𝜌𝑏
𝜀𝑡𝑜𝑡𝑎𝑙 = = 1− = 1−
𝑉𝑏 𝑉𝑏 𝜌𝑡 FLOW DESCRIPTION %COMPRESSIBILITY
Excellent Flow < 10
BULKINESS
Good 11 – 15
• Specific bulk volume
Fair 16 – 20
• Reciprocal of bulk density (ρb)
• Increases with the decrease in particle size Passable 21 – 25
Poor 26 – 31
FREE-FLOWING Very Poor 32 – 37
• Characterized by dustibility Extremely Poor > 38

FLOWABILITY

• The ease with which a powder will flow under a

set of conditions
 HAUSNER RATIO
𝜌𝑡𝑎𝑝𝑝𝑒𝑑
𝐻𝑎𝑢𝑠𝑛𝑒𝑟 𝑅𝑎𝑡𝑖𝑜 =
𝜌𝑏𝑢𝑙𝑘

FLOW DESCRIPTION HAUSNER RATIO

Excellent Flow 1.00 – 1.11
Good 1.12 – 1.18
Fair 1.19 – 1.25
Passable 1.26 – 1.34
Poor 1.35 – 1.45
Very Poor 1.46 – 1.59
Extremely Poor > 1.60

ANGLE OF REPOSE
ℎ𝑒𝑖𝑔ℎ𝑡
𝑡𝑎𝑛𝜃 =
𝑟𝑎𝑑𝑖𝑢𝑠

INTERPRETATION ANGLE OF REPOSE

Excellent 25 – 30
Good 31 – 35
Fair 36 – 40
Passable 41 – 45
Poor 46 – 55
Very Poor 56 – 65
Very, very Poor > 66

• Excellent to Good Flow

o Compressible
• Fair to Passable
o Use glidant or lubricant
• Poor to Extremely Poor
o Use granulation