Micromeritics
Contents of
this chapter
•Definition and concept of micromeritics
•Concept of particle size distribution
• Applications of micromeritics in pharmaceuticals
• Official definition and fineness of powders
• Define Edmundson’s equation
• Concept of particle size distribution curves
• Methods of determination of particle size
• Merits and Demerits of these methods
• Methods of particle size determination – continuation
• Concept of particle shape and surface area
• Methods of determination for particle surface area
• Derived properties of powder
• Concept of moisture content in powders
• Flow properties of powders including angle of repose,
Carr’s index and Hausner’s ratio
• Flow of powder through hopper in tablet press
• Factors influencing flow properties of powder
Learning
Objectives
At the end of this
lecture, student will be able to
• Explain the concept of micromeritics in pharmacy
• Discuss the applications of micromeritics in
pharmaceuticals
• Define the fineness of powder according to Pharmacopoeia
• Discuss the particle size distribution and its impact on
dosage forms
• Explain the concept of micromeritics in pharmacy
• Discuss the applications of micromeritics in
pharmaceuticals
• Define the fineness of powder according to Pharmacopoeia
• Discuss the particle size distribution and its impact on
dosage forms
• Define Edmundson’s equation
• Explain Edmundson’s equation
• Discuss the significance of Edmundson’s equation in
pharmaceutical powders
• Describe the various methods of particle size
determination
• Explain optical microscopy and sieve analysis methods for
determining particle size
• Explain the various methods of particle size determination
• Discuss the concepts and significance of particle shape
and surface area in pharmaceuticals
• Explain the methods for determination of particle surface
area
• Discuss the concepts of derived properties of powders
• Explain the various derived properties of powders
• Discuss the significance of moisture content in powders
and its impact on dosage form development
• Explain the flow properties of powders such as angle of
repose, Carr’s index and Hausner’s ratio
• Discuss the factors influencing flow properties of powder
Micromeritics
• Definition: It
is the science and technology of small particles.
• The unit of particle size is micrometer (µm), micron (µ)
and I micron is equal to 10-6 m
• As particle size decreases â,
surface area increases á
• Micromeritics is the Science and Technology of small
particles.
Knowledge and control of the size and the size range of
particles are important in pharmacy because the size and surface area of a
particle are related to physical, chemical and pharmacologic properties of a
drug.
• The particle size of a drug can affect its release from
dosage forms that are administered orally, parenterally, rectally and
topically.
• In tablet and capsule manufacture, control of the particle
size is essential in achieving the necessary flow properties and proper mixing
of granules and powders.
PARTICLE SIZE AND SIZE DISTRIBUTION
Particle size and analysis
Sieve
Number |
Sieve
opening |
2 |
9.5 mm |
3.5 |
5.6 mm |
4 |
4.75 mm |
8 |
2.36 mm |
10 |
2.00 mm |
20 |
850 µm |
30 |
600 µm |
40 |
425 µm |
50 |
300 µm |
60 |
250 µm |
70 |
212 µm |
80 |
180 µm |
100 |
150 µm |
120 |
125 µm |
200 |
75 µm |
230 |
63 µm |
270 |
53 µm |
325 |
45 µm |
400 |
38 µm |
PARTICLE
SIZE |
EXAMPLE
(µm) |
0.5 to 10 |
Suspension, Fine emulsion |
10 to 50 |
Coarse emulsion |
50 to 100 |
Fine powder |
100 to 1000 |
Coarse powder |
1000 to 3350 |
Average granule size |
Powders of vegetable and animal drugs are officially defined
as follows:
- Very coarse (No. 8): All particles pass through a No. 8
sieve (2.36 mm) and not more than 20% through a No. 60 sieve (250 µm).
- Coarse (No. 20):
All particles pass through a No. 20 sieve (850 µm) and not more than 40%
through a No. 60 sieve.
- Moderately coarse
(No. 40): All particles pass through a No. 40 sieve (425 µm) and not more than
40% through a No.80 sieve (180 µm).
- Fine (No. 60): All
particles pass through a No. 60 sieve (250 µm) and not more than 40% through a
No. 100 sieve (150 µm).
- Very fine (or a
No. 80): All particles pass through a No. 80 sieve. There is no limit to
greater fineness.
The powder fineness for chemicals is defined as follows
• Course (or a No. 20) powder-All particles pass through a
No. 20 sieve and not more than 60% through a No. 40 sieve
• Moderately Course (or a No. 40) powder-All particles pass
through a No. 40 sieve and not more than 60% through a No. 60 sieve
• Fine (or a No 80) powder-All particles pass through a No.
80 sieve. There is no limit as to greater fineness
• Very fine (or a No. 120) powder-All particles pass through
a No. 120 sieve. There is no limit as to greater fineness
• Granules typically fall within the range of 4（4.75
mm) to 12- sieve size, although granulations of powders prepared in the 12- to
20-sieve (850 µm) range are sometimes used in tablet making.
• The purpose of particle size analysis in pharmacy is to
obtain quantitative data on the size, distribution, and shapes of drug and
nondrug components to be used in pharmaceutical formulations.
Particle Size and Size Distribution
• In a collection of particles of more than one size, two
properties are important, namely.
1. The shape and surface area of the individual particles.
2. The particle size and size distributions (The size range
and number or weight of particles).
Particle Size
• The size of a sphere is readily expressed in terms of its
diameter.
• The Surface diameter, d_{s}, is the diameter of
a sphere having the same surface area as the particle.
• The Volume diameter, d_{v}, is the diameter of
a sphere having the same volume as the particle.
• The Projected diameter, d_{p}, is the projected
diameter of a sphere having the same observed area as the particle.
• The Sieve diameter, d_{sieve}, is the diameter
which describes an equivalent sphere that pass through the same sieve aperture
as the asymmetric particle.
• Any collection of particles is usually Polydisperse. It is
therefore necessary to know not only the size of a certain particle, but also
how many particles of the same size exist in the sample
• Thus, an estimate of the size range present and the number
or weight fraction of each particle size is required.
• This is the particle-size distribution and from it an
average particle size for the sample can be calculated.
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, a
so- called Frequency distribution curve is obtained.
• This is important because it is possible to have two
samples with the same average diameter but different distributions.
Applications of Micromeritics
1. Release and dissolution
2. Absorption and drug action
3. Physical stability
4. Dose uniformity
Release and dissolution
• Particle size and surface area influence the release of a
drug from a dosage form.
• Higher surface area allows intimate contact of the drug
with the dissolution fluids in vivo and increases the drug solubility and dissolution.
Absorption and drug action
• Particle size and surface area influence the drug
absorption and subsequently the therapeutic action.
• Higher the dissolution, faster the absorption and hence
quicker and greater the drug action
Physical stability
• The particle size in a formulation influences the physical
stability of the suspensions and emulsions.
• Smaller the size of the particle, better the physical
stability of the dosage form.
Dose uniformity
Good flow properties of granules and powders are important in
the manufacturing of tablets and capsules.
Edmundson’s Equation
d _{mean} = (Σnd^{p+f}/ Σnd^{f})^{1/p}
Where “n” is number of particles in each size range
“d” is the diameter of a particle in a given size range
“f” is the frequency factor
p is the index of size;
values of 1, 2 and 3 (p = 1 gives particle length, p = 2
gives particle surface and p = 3 gives particle volume)
Factor Affecting Particle size
Particle size can influence
a variety of important factors, including:
1) Dissolution rate of particles intended to dissolve; drug
micronization can increase the rate of drug dissolution and its
bioavailability.
2) Suspendability of particles intended to remain
undissolved but uniformly dispersed in a liquid vehicle (e.g., fine dispersions
have particles approximately 0.5-10 µm).
3) Uniform distribution of a drug substance in a powder mixture
or solid dosage form to ensure dose-to-dose content uniformity.
4) Penetrability of particles intended to be inhaled for
deposition deep in the respiratory tract (e.g., 1-5 µm).
5) Lack of grittiness of solid particles in dermal
ointments, creams, and ophthalmic preparations (e.g., fine powders may be
50-100µm in size).
Particle size Distribution
Size Range (Microns) |
Mean Size Range |
No. of particles in each range |
% frequency no. of particles |
% frequency weight distribution |
1-10 |
11 |
18 |
6 |
1.75 |
10-20 |
31 |
60 |
20 |
13.17 |
20-30 |
45 |
56 |
19 |
27.78 |
30-40 |
54 |
40 |
13 |
12.31 |
40-50 |
61 |
10 |
5 |
12.53 |
Particle size Distribution curves
• Two powder samples may have same mean size, but different
in the size distribution above and below the mean
• Such differences are observed from frequency distribution
curves
• Frequency distribution curves are the one obtained when particle
size is plotted against frequency
• They are of FOUR types namely
– Frequency distribution curve Log
– Normal distribution curve
– Cumulative frequency distribution curve
– Log – probability plot
Average Particle Size
Frequency distribution curve
• The curve is Symmetrical/ Bell shaped
• Positive and negative deviations from the mean are uniform
• Not found in pharmaceutical powders
Particle Size Distribution
• Frequency
distribution curve
• The curve is Asymmetric/ Skewed
• Positive and negative deviations from the mean are not
uniform
• Long tail of larger particles
• Cumulative
frequency distribution curve
• The curve is sigmoidal curve with the mode
• Particle size at the greatest slope
• Percentage of particles cane be found within any given
size range
• But scattering of points cannot be identified
• Log-normal
distribution curve
• The distribution pattern is made Symmetrical, when
compared to normal distribution curve
• Powders obtained by crystallization and milling methods
exhibits this pattern
• Log-probability
plot
• The cumulative curve is converted into a straight line
• Slope is determined which gives geometric standard deviation
• Reference point gives geometric mean diameter
• Not used much in Pharmacy
• Number of particles per unit weight
e.g. if particle = sphere
Methods for determining particle size
• Many methods available for determining particle size such
as optical microscopy, sieving, sedimentation and particle volume measurement.
1. Optical microscopy (range: 0.2-100 µm).
2. Sieving (range: 40-9500 µm).
3. Sedimentation (range: 0.08-300 µm).
4. Particle volume measurement (range: 0.5-300 µm).
5. LALLS method (Low Angle Laser Light Scattering method)
Range of particle size
A guide to range of particle sizes applicable to each method
is
Particle size |
Method |
1 µm |
Electron microscope, ultracentrifuge, adsorption |
1 – 100 µm |
Optical microscope, sedimentation, coulter counter, air permeability |
> 50 µm |
Sieving |
Calibration of Eyepiece Micrometer
Each eyepiece
division on the eyepiece micrometer is equivalent to
Number of divisions
of stage micrometer
=
----------------------------------------------------------- X 10
Number of divisions of eyepiece micrometer
• Determination of particle size
• Remove stage micrometer, retaining the eyepiece micrometer
on the microscope
• Place the powder sample on a clean glass slide and spread
uniformly
• Place the slide under microscope and observe
• By rotating the nose piece of the microscope count and
measure the length and breadth of 100 particles
• Plot a graph between class interval and cumulative frequency
oversize and undersize
Optical microscopy
The microscope eyepiece is fitted with a micrometer by which
the size of the particles may be estimated.
Optical microscopy (range: 0.2-100 µm)
• According to the optical microscopic method, an emulsion
or suspension is mounted on ruled slide on a mechanical stage.
• The microscope eyepiece is fitted with a micrometer by
which the size of the particles can be estimated.
• The ordinary microscope used for measurement the
particle-size in the range of 0.2 to about 100 µm.
• Based on number distribution of different particle size
• Range: 0.2 - 100µm
• >200 counts (300-500 counts)
• Optical microscopy (range: 0.2 –100 um):
• The microscope eyepiece is fitted with a micrometer by
which the size of the particles may be estimated
Disadvantage of microscopic method
1. The diameter is obtained from only two dimensions of the
particle.
2. The number of particles that must be counted (300-500) to
obtain a good estimation of the distribution makes the method somewhat slow and
tedious.
Sieve Analysis
• This method uses a series of standard sieves
• Range: 44 - 1000µm
Sieve
• Mesh number: number of openings per inch
• Sieve opening: actual size of openings between wires
Sieve number |
Aperture size micrometer |
10 |
1700 |
12 |
1400 |
16 |
1000 |
22 |
710 |
30 |
500 |
36 |
425 |
44 |
325 |
60 |
250 |
85 |
36 |
100 |
35 |
120 |
34 |
150 |
32 |
For a Powder passing through Sieve no. 44 and retained on
Sieve no.60, the particle size will be 325+250/2 = 287.5 microns
Sieve Analysis (Range: 40-9500 µm)
• Standard size sieves are available (IP and USP
specifications) to cover a wide range of size.
• These sieves are designed to sit in a stack so that
material falls through smaller and smaller meshes until it reaches a mesh which
is too fine for it to pass through.
• Coarsest at top and finest at bottom
• The stack of sieves is mechanically shaken to promote the
passage of the solids.
• The fraction of the material between pairs of sieve sizes
is determined by weighing the residue on each sieve.
• The result achieved will depend on the duration of the
agitation and the manner of the agitation.
• Particles are passed by mechanical shaking through a
series of sieves of known and successively smaller size
• The determination of the proportion of powder passing
through or being withheld on each sieve (range about 40-9500µm, depending upon
sieve sizes).
Disadvantages
• Lower limit of particle is 40 microns
• Powder should be dry; if not will clog the mesh
• During shaking size reduction may happen; which leads to
errors in estimation
Sedimentation Method
(Range: 1-200 µm)
• By measuring the terminal settling velocity of particles
through a liquid medium in agravitational centrifugal environment using
Andreasen appartus.
• The diameter is obtained by gravity sedimentation
• Prepare 2% suspension of light magnesium oxide containing 0.2%w/v
polyvinyl pyrollidone as deflocculating agent
• Pour the suspension into Andreasen pipette and make up the
volume to 550ml with purified water
• Note the height of suspension in Andreasen pipette
• Pipette out 10ml of sample from Andreasen pipette and
transfer to a tarred china dish
• Evaporate the contents of china dish till the residue is
obtained
• Weigh china dish and note the weight
• The difference in weight will give the fraction of solid
collected at given time interval
• Repeat the process at the interval of every 5 minutes and
continue up to 30 minutes
Sedimentation
Stoke’s law
Where
v: rate of settling
h: distance of fall in time t
r_{s}: density of particle
r_{0}: density of dispersion medium
g: acceleration due to gravity
h_{0}: viscosity of medium
Reynolds number R_{e}
• R_{e} > 0.2 à
Stoke’s law cannot be used
• Flow should be laminar and not turbulent
• Suspension should be dilute (1 -2%)
Particle volume measurement – Coulter Counter
(Range: 0.5-300 µm)
• In this type the powder is suspended in an electrolyte
solution
• This suspension is then made to flow through a short
insulated capillary section between two electrodes and the resistance of the
system is measured.
• When a particle passes through the capillary there is a
momentary peak in the resistance, the amplitude of the peak is proportional to
the particle size.
• Counting is done by a computer.
Coulter Counter
LALLS METHOD
• LALLS – Low Angle Lase Light Scattering Technique
PARTICLE SHAPE AND SURFACE AREA
Specific Surface
• The surface area per unit weight (S_{w})
d = diameter of particles
Ρ = density of powder
METHODS FOR DETERMINING SURFACE AREA
Adsorption Method
• The volume in cubic centimeters of gas adsorbed per gram
of adsorbent may be plotted against the pressure of the gas at constant
temperature
• Using Solute
Powder sample + Methanolic solution of magnesium stearate
----- Mix for 1 hour -----Filter ----- Filtrate contains unadsorbed stearic
acid ---- Estimate this by titrating with sodium hydroxide -- Calculate the
adsorbed stearic acid/gm of powder using Avagadro’s number (6.023X1023), by
which no.of molecules/gm can be calculated ----- If area occupied by one molecule is known,
then the total surface area occupied by all molecules can be calculated which
gives the Total Surface Area of the given powder sample
• Using Adsorption of
Gas - QUANTASORB
Powder sample placed in a cell ----- Pass Nitrogen and
Helium gas ----- Amount of nitrogen adsorbed at every equilibrium pressure was
measured using thermal conductivity detector ------- BELL shaped curve will be
obtained ------ Signal height gives the rate of adsorption of nitrogen gas and
AUC give amount of nitrogen gas adsorbed in 1cm3 on powder sample using BET
equation
P 1 (b-1)P
--------- =
------ + ----------
V(P_{0}-P) Vmb VmbP_{0}
• V = volume of gas in 1cm^{3} adsorbed/gm of powder
at pressure P
• P0 = saturated vapour pressure of nitrogen gas
• b = constant that gives difference between Heat of
adsorption and Heat
Air Permeability
Method
• The principle resistance to the flow of a fluid, such as
air, through a plug of compressed powder is the surface area of the powder
• The flow rate through the plug, or bed, is affected by
– The degree of compression of the particles
– The irregularity of the capillaries
FISHER SUB SIEVE SIZER
• Based on Porosity
• As porosity decreases, surface area powder also increases
• When air is passed through the plug, resistance to flow
occurs
• This resistance is related to surface area, which is
determined by Kozency-Carman equation
v= A Ù pt Ɛ^{3}/ƞS^{2}w.
Kl. (1-Ɛ)2
A- C.S area of plug s- specific surface
K - Constant ( 5±0.5) v – volume of air
that flowed in time‘t’
ƞ – viscosity of air
Ɛ – Porosity t – time of flow in secs
Ùp - pressure
difference, l =
length of sample holder
Derived Properties of Powders
• Porosity
• Packing arrangement
• Densities of particles
• Bulkiness
• Flow properties
• Compaction
Porosity (e)
• Void volume (v): the volume of space
• Bulk volume (V_{b}) : occupied volume
• True volume (V_{p})
• Porosity = Bulk volume – True volume / Bulk volume
(OR)
• Porosity = True density – Bulk density / True density
• Pharmaceutical powders should possess 30-50% porosity
Packing Arrangements
• Two ideal packing materials
1. Closest or rhombohydral
2. Most open, loosest or cubic packing.
• Theoretical porosity of powder consist of uniform sphere
in
• Closest packing- 26%
• Loosest packing- 48%
• Real powder have porosity in between 30 to 50%.
• In suspension, porosity may above the theoretical max
limit 48%.
• Crystalline materials porosity- <1% (under force 10000
lb/in2)
Densities of Particles
True density (r)
• Density of the actual solid material. Ratio of given mass
of powder and its true volume
• True volume = Bulk volume – Void volume
• Determined by Liquid displacement method
Granule density (r_{g}) (Particle density)
•The mass of particles divided by the volume as determined
by the Mercury displacement method
True density measurements-
• For non-porous solid
- True density & granule density identical.
- Both obtained by-
- Helium displacement method
- Liquid displacement method
• For porous material (having an internal surface)
- Using helium densitometer
Bulk density
Bulk density = mass of the powder (w) / bulk volume (Vb)
• When particle are loosely packed, lots of gaps in between
particle.
• Bulk volume increases making powder light.
• Powder classified as ‘light’or ‘heavy’ “light powder have
high bulk volume”
• ‘Bulk density apparatus’ is used to determine bulk volume.
Applications:-
• Used to check uniformity of bulk chemicals.
• Size of capsule determine by bulk volume.
• Higher the bulk volume bigger the size of capsule.
Densities of Particles
• During tapping, particles gradually pack more efficiently,
the powder volume decreases and the tapped density increases.
Moisture Content
• Higher the moisture content greater the cohesion &
adhesion.
• Flow properties can be improved by following methods-
Powder processes into granules to improve flow.
• Choosing optimum size of granules (400 to 800 um)
• Incorporating optimum amount of fines (about 15%)
• Incorporating optimum concentration of lubricants (magnesium
stearate, talc)
Bulkiness
• Bulkiness (bulk) is specific bulk volume, the reciprocal
of bulk density
• It is an important consideration in the packaging of
powders.
• The bulk density of calcium carbonate vary from 0.1 to
1.3, and the lightest (bulkiest) type require a container about 13 times larger
than that needed for the heaviest variety.
• Bulkiness increases with a decrease in particle size
• In mixture of materials of different sizes, the smaller
particles sift between the larger ones and tend to reduce bulkiness.
Light vs. Heavy Powders
• Light: low bulk density or large bulk volume
• Heavy: high bulk density or small bulk volume
Flow Properties
• A bulk powder is somewhat analogous to a non-Newtonian liquid
(plastic flow, dilatancy)
• Flow property is affected by particle size, shape,
porosity, density, surface texture
• Measurement: angle of repose (f) (= f(roughness))
tan f = m
• m: coefficient of friction
Non-uniformity (segregation) in blending
Angle of repose
• The angle of repose is a relatively simple technique for
estimating the flow properties of a powder.
• It can easily be determined by allowing a powder to flow
through a funnel and fall freely onto a surface
• The height and diameter of the resulting cone are measured
and the angle of repose calculated from this equation:
tanf=h/r
Where
h is the height of the powder cone
r is the radius of the powder cone.
• The sample is poured onto a horizontal surface and the
angle of the resulting pyramid is measured.
The user normally selects the funnel orifice through which
the powder flows slowly and reasonably constantly.
• Angle of repose less than 20 (excellent flow)
• Angle of repose between 20-30 (good flow)
• Angle of repose between 30-34 (Pass flow)
• Angle of repose greater than 40 (poor flow)
• The rougher and more irregular the surface of the
particles, the higher will be the angle of repose.
Porosity, void, and bulk volume
• The characteristics used to describe powders include
porosity, true volume, bulk volume, apparent density, true density, and bulkiness.
Porosity is void x 100%
• This value should be determined experimentally by
measuring the volume occupied by a selected weight of a powder, V_{bulk}.
• The true volume, V, of a powder is the space occupied by
the powder exclusive of spaces greater than the intramolecular space.
Void can be defined as
(V_{bulk}-V)/V_{bulk}
• Therefore, porosity is (V_{bulk}-V)/V_{bulk}x100%
• The bulk volume is true volume + porosity
Apparent density (Bulk), true density, and bulkiness
• The apparent (bulk) density, r_{a},
is
• Weight of the sample/V_{bulk}
• The true density, r, is
• Weight of the sample/V
• The bulkiness, B, is the reciprocal of the apparent
density,
B=1/ r_{a}
Carr’s compressibility index
• A volume of powder is filled into a graduated glass
cylinder and repeatedly tapped for a known duration. The volume of powder after
tapping is measured.
• Carr’s index (%) = Tapped density –
Poured or bulk density x 100
Tapped density
• Bulk density = weight / bulk volume
• Tapped density = weight / true volume
Relationship between powder flowability and % compressibility
Flow
description |
%
compressibility |
Excellent flow |
5 – 15 |
Good |
16 – 18 |
Fair |
19 – 21 |
Poor |
22 – 35 |
Very poor |
36 – 40 |
Extremely poor |
> 40 |
Hausner ratio
Hausner ratio = Tapped density / Poured or bulk density
• Hausner ratio was related to interparticle friction:
• Value less than 1.25 indicates good flow (= 20% Carr).
• The powder with low interparticle friction, such as coarse
spheres.
• Value greater than 1.5 indicates poor flow (= 33% Carr).
• More cohesive, less free-flowing powders such as flakes.
• Between 1.25 and 1.5, added glidant normally improves flow.
• > 1.5 added glidant doesn’t improve flow.
Dispersibility
• It is the ability of a material to flow or pour easily
over a planes.
• Dispersability, dustiness, & floodability are inter-
related term.
weight of powder in
watch glass
Dispersability (%) = ----------------------------------------------
ˣ 100
initial
weight of the sample
Dispersibility apparatus:-
• A hallow cylinder through which is Drop from a height 61
cm above the glass watch.
Compression Properties
• This property normally used for the preparation of the tablet.
• This process also called compaction.
• During this porosity of powder changes.
• Plastic behaviour:-
- Deformed on compression
- Compact powder get deformed which is tapped into close
packing.
- For e.g. kaolin which have soft & spongy particle
• Dilatant behaviour:-
- Shows unexpected expansion under the stress.
- Some substances when compacted exhibits higher porosity
than the powder in close packing.
• For e.g. sodium chloride.
• Compression properties of most drugs extremely poor.
• Hence compression vehicle is added such as-
1) Lactose
2) Calcium
phosphate
3) Microcrystalline
cellulose
• Low dose drug tablet prepared by direct compression
• But high dose drug prepared by granulation methods.
• Tablet material should be plastic i.e. undergoing
permanent deformation
Flow Through Orifice Powder flow meter
Factors affecting the flow properties of powder
1. Alteration of
Particle’s size & Distribution
2. Alteration of
Particle shape & texture
3. Alteration of
Surface Forces
4. Formulation
additives (Flow activators)
Alteration of Particle’s size & Distribution
• There is certain particle size at which powder’s flow
ability is optimum.
• Coarse particles are more preferred than fine ones as they
are less cohesive.
• The size distribution can also be altered to improve
flowability by removing a proportion of the fine particle fraction or by
increasing the proportion of coarser particles such as occurs in granulation.
Alteration of Particle shape & texture
Particle’s Shape
• Generally, more spherical particles have better flow
properties than more irregular particles.
• Spherical particles are obtained by spray drying, or by temperature
cycling crystallization.
Particle’s texture
• Particles with very rough surfaces will be more cohesive
and have a greater tendency to interlock than smooth surfaced particles.
Alteration of Surface Forces
• Reduction of electrostatic charges can improve powder
flowability.
• Electrostatic charges can be reduced by altering process
conditions to reduce frictional contacts.
• Moisture content of particle greatly affects powder’s
flowability.
• Adsorbed surface moisture films tend to increase bulk
density and reduce porosity.
• Drying the particles will reduce the cohesiveness and
improve the flow.
• Hygroscopic powder’s stored and processed under low humidity
conditions.
Formulation additives (Flow activators)
• Flow activators are commonly referred as a glidants.
• Flow activators improve the flowability of powders by
reducing adhesion and cohesion.
e. g. Talc, maize starch and magnesium stearate.
METHODS OF IMPROVING FLOW PROPERTIES
• Increasing the average particle size
• By producing the powder in the form of spherical particles
• By use of additives
INCREASING THE AVERAGE PARTICLE SIZE
• The larger particles are less cohesive than smaller ones
and the optimum size for free flow exists and also a distinct disadvantages in
using a finer grade is noted.
• Hence granules are used in many cases than powder forms
and also the addition of coarser fraction to fine powder improves its flow
property.
BY PRODUCING THE POWDER IN THE FORM OF SPHERICAL PARTICLES
• By using this type of powder, it packs down and flows
easily since particles roll over one another.
BY USE OF ADDITIVES
• Commonly used additives to increase the flow properties of
the powders are flow enhancers
• They are generally used in low conc’s and the optimum conc
of all glidants varies from 1% to 2% and above this conc, the flow properties
of powders decreases.
Various mechanisms of glidant action
• Dispersion of static charge from surface of host particles
• Distribution of glidants in host particles
• Adsorption of gases and vapours are adsorbed onto host
particles
• Physical separation of particles and reduction in
vanderwaal’s interaction.
• Adsorption of glidant particles to granulation surfaces so
that friction between particles and surfaces are minimized.
• The effect of glidant depends on may factors such as…
1, Physical & chemical affinity of powder
2, Average particle size & shape
3, Concentration of glidant
4, Degree of mixing
5, Moisture content
• Glidants generally has mechanical action …they adhere to
surface of host powders and reducing their tendency to interlock mechanically
during movement and flow.
• In general 100µm powder requires about 3% of 1 µm glidant
Summary
• Micromeritics is defined as the science and technology of
small particles.
• The unit of particle size used in the micrometer (µm),
micron (µ) and equal to 10-6 m.
• The particle size of a drug can affect its release from
dosage forms that are administered orally, parenterally, rectally and topically
• Particle size
is expressed as Surface diameter, Volume diameter, projected diameter and
Stokes diameter.
• Micromeritics
has applications in drug release and dissolution, absorption and drug action,
Physical stability and dose uniformity.
• d mean = (Σndp+f/ Σndf)1/p - Edmundson’s Equation
• Particle size
distribution curves including
- Frequency distribution curve
- Cumulative percent curve
- Log normal distribution curve
- Log probability curve
• Various methods of
particle size determination including
- Optical microscopy (range: 0.2-100 µm).
- Sieving (range: 40-9500 µm).
- Sedimentation (range: 0.08-300 µm).
- Particle volume measurement (range: 0.5-300 µm).
- LALLS method (Low Angle Laser Light Scattering method)
• Particle size can
be determined by Sedimentation, Particle volume measurement and LALLS
method (Low Angle Laser Light Scattering method)
• Specific surface
area is determined by Air permeability and Adsorption method
• Fischer Sub sieve
sizer is used to determine particle
surface area
• Various derived
properties of pharmaceutical powders include Porosity, Packing arrangement,
Densities of particles Bulkiness, Flow properties and Compaction
• Role of angle of repose,
Carr’s index and Hausner’s ratio has been discussed with emphasis on dosage
form development
• Significance of moisture content in powders and its impact
on dosage form development was discussed
• Factors that
influence pharmaceutical powders are Alteration of Particle’s size &
Distribution, Alteration of Particle shape & texture, Alteration of Surface
Forces and Formulation additives (Flow activators)
• Flow properties
can be enhanced by increasing the
average particle size, by producing the powder in the form of spherical
particles and by use of additives
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