2. Contents
Introduction to Micromeritics
Particle size distribution
Methods to determine particle size
Derived properties of powder
Factors affecting flow properties of powder
Application of micromeritics
Case study and the protocol
3. Micromeritics
• Definition: It is the science and technology of small
particles.
• Control of the size and the size range of particles are
significant importance in pharmacy because the size and
surface area of the particles related to the physical,
chemical and pharmacological properties of drug.
• The unit of particle size used in the micrometer (μm),
micron (μ) and equal to 10⁻⁶ m.
• As particle size decreases, area increases.
4. Particle Size in Pharmaceutical Dispersions:
Sr. No. Particle Size Examples
1. 0.5-10μm Suspension and Fine Emulsion
2. 10-50μm Coarse Emulsion Particles,
Flocculated Suspension
3. 50-100μm Fine Powder Materials
4. 150-1000μm Coarse Powder Range
5. 1000-3360μm Granules
5. Particle size Distribution
• When the number or weight of particles lying within a
certain size range is plotted against the size range or
mean particle size the frequency distribution curve is
obtained.
• This is important because it is possible to have two
samples with the same average diameter but different
distributions.
8. 1. Optical Microscopy
According to optical microscopic method, an emulsion or
suspension, diluted or undiluted is placed on the slide
which is then mounted on a mechanical stage.
The eye piece has a micrometer scale by which the particle
size can be measured.
This method is used for the particle size measurement in
the range between 0.2- 100μm.
The particle size can be determined in terms of various
diameter as shown in Fig.2.
9. Fig.2.Optical Microscopy
1. Martin’s diameter: Is the length of line that bisect the particle
image. The line can be drawn in any direction, but must be in the
same direction for all particle measurement.
2. Feret’s Diameter: Is the distance between two tangent on
opposite site sides of particle parallel to same fixed direction.
3. Projected Area Diameter: Is the diameter of circle with same
area as that of particles.
10. Disadvantages
• This method gives diameter of particles in 2D image. the
length, width and thickness of the particles can’t be
determined.
• The no. of particles that must be counted are in the range
of 300-500 to obtain a good estimation. Thus the method
is slow.
11. 2. Sieving/ Sieve Analysis
(range: 40-9500μm)
• According to the method of US Pharmacopoeia for
testing fineness of powder, the sieves are arranged in
nest with coarsest sieve on the top i.e. the smallest sieve
no. at the top.
• A carefully weighed sample of powder is placed on the
topmost sieve and then the sieve are shaken for
predetermined period of time.
• The powder retained on each sieve is then weighed and
the right distribution curve of powder sample can be
plotted.
12. Disadvantage:
• In this technique, if the vigorous shaking is done, the
particle may break leading to generation of time and
creating errors in the result.
13. 3. Sedimentation (Range: 0.08-300μm)
• In this method the terminal settling velocity of particles
through a sample medium in gravitational centrifugal
environment is to be measured by Andreasen Apparatus.
• This method is based on Stoke’s law,
V= h/t = 𝑑2
( ƍ - ƍo ).g
18 ɳo
V = Velocity of settling
h = Distance of fall of particle in time ‘t’
d = Mean diameter of particle based on velocity of sedimentation
ƍ = Density of particle
ƍo = Density of dispersion medium
g = Acceleration due to gravity
ɳo = Viscosity of dispersion medium
14. Fig.3. Andreasen Apparatus
It consist of 550 ml vessel containing
10 ml pipette placed in cylinder its
lower tip is 20 cm below the surface
of suspension.
15. Particle Volume Measurement
( Range: 0.5-300μm)
• This instrument operates on the principle that when a
particle is suspended in conducting liquid passes
through a small orifice on side of electrode, a change in
electric resistance occurs.
17. Derived Properties Of Powder
• Porosity
• Packing Arrangement
• Densities of Powder
• Bulkiness
18. 1. Porosity:
V= Vb - Vp
• Bulk Volume (Vb)
• True Volume (Vp)
It is defined as ratio of void volume to the bulk volume
Expressed by equation,
ϵ = Vb – Vp/ Vb = 1 – Vp/Vb
2. Packing Arrangement :
Two types of packing arrangements-
I. Closest or rhombohedral packing
II. Open or Loosest packing
19. 3. Bulkiness :
The reciprocal of bulk density is called as bulkiness.
It plays an important role in packing of the powders.
As the bulkiness increases with decrease in particle size.
20. Factors affecting flow properties of
powders
• Particle Size
• Shape of particles
• Density
• Surface texture
21. Application of Micromeritics
1. Release and Dissolution:
Particle size and surface area influences the release of
drug from dosage form.
Higher surface area allows intimate contact of the drug
with the dissolution fluids in vivo and increase the drug
solubility and dissolution.
2. Absorption and Drug action:
Particle size and surface area influences the drug
absorption and subsequently the therapeutic action.
Higher the dissolution, faster the absorption and hence
quicker and greater the drug action.
22. 3. Physical Stability:
The particle size in a formulation influences the physical
stability of the suspension and emulsion.
Smaller the size of particles, better the physical stability of
dosage form.
4. Dose Uniformity:
Good flow properties of granules and powders are
important in the manufacturing of tablet and capsules.
24. ABSTRACT
The present study enlightens to enhance the dissolution
profile, absorption efficiency and bioavailability of water
insoluble drugs like lovastatin. A novel “Powder Solution
Technology” involves absorption and adsorption efficiency,
which makes use of liquid medications admixed with
suitable carriers and coating materials and formulated into
a free flowing, dry looking, non adherent and compressible
powder forms. Based upon a new mathematical model
expression improved flow characteristics and hardness of
the formulation has been achieved by changing the
proportion of carrier and coating material.
25. MATERIAL AND METHODS
MATERIAL
Lovastatin conc. in PEG, Micro crystalline cellulose, Aerosil,
Crospovidone, Sodium starch glycolate, Magnesium stearate
METHODS
1. Angle of repose
The angle of repose physical mixtures of liquisolid compacts
were determined by fixed funnel method. The accurately
weighed physical mixtures of liquisolid compacts was taken in a
funnel. The height of the funnel was adjusted in such a way that
the tip of the funnel just touches the apex of the heap of the
powder. The powder was allowed to flow through the funnel
freely into the surface. The height and diameter of the powder
cone was measured and angle of repose was calculated.
Tanθ= h/r
Where, θ is the angle of repose
h is the height in cms
r is the radius in cms
.
26. Standard Values for Angle of Repose
25-30 Excellent flow
31-35 Good flow
36-40 Fair flow
41-45 Passable flow
27. 2. Bulk Density
The loose bulk density and tapped density were determined by
using bulk density apparatus. Apparent bulk density was
determined by pouring the blend into a graduated cylinder. The
bulk volume (Vb) and weight of the powder (M) was determined.
The bulk density was calculated using the formula,
Db =M/Vb
Where, M is the mass of powder
Vb is bulk volume of powder
3. Tapped Density
The measuring cylinder containing a known mass of blend was
tapped for a fixed time. The minimum volume (Vt) occupied in the
cylinder and the weight (M) of the blend was measured. The
tapped density was calculated using the formula,
Dt = M/Vt
Where, M is the mass of powder
Vt is tapped volume of powder
28. 4. Carr’s Index (%)
The compressibility index has been proposed as an indirect
measure of bulk density, size and shape, surface area,
moisture content and cohesiveness of material because all
of these can influence the observed compressibility index.
The simplest way for measurement of free flow of powder
is Carr’s Index, a indication of the ease with which a
material can be induced to flow is given by Carr’s index (I)
which is calculated as follows:
CI (%) = [(Tapped density – Bulk density) / Tapped
density]x100
1-10 % Excellent flow
Characteristic
11-15% Good flow
16-20% Fair to passable
21-25% Passable
29. 5. Hausner’s ratio
Hausner’s ratio is an indirect index of ease of powder flow.
It is calculated by the following formula.
Hausner’s Ratio=Tapped density / Bulk density
Standard Values of Hausner’s ratio:
Less than 1.25 Better flow
1.25 to 1.5 Moderate flow
More than 1.5 Poor flow
30. RESULTS AND DISCUSSION:
F1, F3, F5 and F7 angle of repose is between 30ᵒ to 35ᵒ. carr’s index range
between 12 to 15. Housner’s ratio1.12 to 1.18. it indicates the good flow
properties. F2,F4 and F6 angle of repose in between 35ᵒ to37ᵒ. Carr’s index
Between 16 to 20. Housner’ratio1.19 to 1.25. It indicates passable flow
properties.
Parameters F1 F2 F3 F4 F5 F6 F7
Angle of
repose
33.1±0.2 37.9±0.7 35.5±0.6 37.9±0.7 35.5±0.6 37.9±0.7 33.1±0.2
Bulk
density
(gm/cc3)
206.5±1.6 303.7±1.6 308.3±1.4 303.7±1.6 308.3±1.4 303.7±1.8 308.3±1.4
Tapped
density
(gm/cc3)
235.7±0.2 379.6±1.2 359.7±1.6 379.6±1.2 359.7±1.6 379.6±1.4 359.7±1.6
Carr’s
index(%)
12.5±0.6 19.9±0.3 14.2±0.3 19.9±0.3 14.2±0.3 19.9±0.5 14.2±0.3
Hausner’s
ratio
1.14±0.02 1.24±0.02 1.16±0.01 1.24±0.02 1.16±0.01 1.24±0.01 1.14±0.04
31. CONCLUSION
• The present study gives an idea about the determination
or evaluation of micromeritic properties of lovastatin
drug and the basic idea about the methods which were
used to determine the particle size of powder and the
granules. Also the flow properties and the factors which
affect on the flow of the powders and granules.
32. References
1. Martin’s Physical Pharmacy and Pharmaceutical
Sciences, Patrick J. Sinko, Sixth Edition.
2. Y. Divya bharathi and V. B. Rajesh, World Journal of
Pharmaceutical Research, Enhancement Solubility of
Lovastatin Drug by using liqui-solid technique, volume
6, issue 17, 567-587.
