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Note -If You have any Doubts

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in any thing in pdf

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Just Ask us in comment of any video,

Or confirm it from google

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MICROMERITICS

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Definition:
Micromeritics is the science and technology of small particles. Knowledge and control of the
size and the size range of particles are of significant importance in pharmacy because the size
and surface area of a particle related to the 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,
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parenterally, rectally and topically.
In the area of tablet and capsule manufacture, control of the particle size is essential in achieving
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the necessary flow properties and proper mixing of granules and powders.
Applications:
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1. Release and dissolution.
2. Absorption and drug action.
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3. Physical stability.
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4. Dose uniformity.
1. Release and dissolution.
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Particle size and surface area influence the release of a drug from a dosage form. Higher surface
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area allows intimate contact of the drug with the dissolution fluids in vivo and increases the drug
solubility and dissolution.
2. 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.
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3. Physical stability
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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.
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4. Dose uniformity.
Good flow properties of granules and powders are important in the manufacturing of tablets and
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capsules.
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Particle size and size Distribution: When a powder sample contains of uniform size, it is said
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to be monodisperse. In collection of particles of more than one size, it is said to be polydisperse.

The pharmaceutical powders are almost always be polydisperse and hence it is necessary to
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charcterise particle size and their distribution. For characterisation two properties are important
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i.., (a) the shape and surface area of the individual particles, and (b) the size range and number
or weight of particles present and hence, the total surface area. The size of a sphere can
completely be expressed in terms of its diameter. When particle is asymmetrical the diameter
which is related to an equivalent spherical diameter, which relates the size of the particles to the
diameter of a sphere having the same surface area, volume or diameter
The size of particles may be expressed as:
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) Surface diameter, ds : Is the diameter of a sphere having the same surface area as that of the

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asymmetric particle.
(i) Volunme diameter, dv : Is the diameter of of a sphere having same volume as that of the
asymmetric particle.
(ii) Projected diameter, dp : Is
the diameter of sphere having the same observed area as the
particle when viewed normal to its most stable plane.
(iv) Stokes'diameter, dst: Is the diameter of an equivalent sphere undergoing sedimentation at
a

a
the same rate as the asymmetric particle.
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(Sieve diameter, d sieve: Is the diameter of a sphere that will just pass through the same
square or sieve aperture as the particle.
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(vi) Volume-surface diameter; dvs: Is the diameter of a sphere that has the same volume to
surface area ratio as the asymmetric particle.
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Frequency distribution curve:
In this type, number or weight of particles lying within particular size range is plotted against the
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mean particle size. In general the normal distribution curve is expected to be symmetrical (bell
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shaped) around the mean, which is also the mode. In this type of distribution, the positive and
negative deviations from the mean are uniform and it is represented by standard deviation.
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Larger particles obtained by granulation can be described by normal distribution. In this case,
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arithmetic mean and standard deviation are considered.
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.
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3-2- 0 tT t2g +3a

L
13 14 15 16 17
8 9 10 11 12
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Particle size (log mean)
iS tne
gure 6-2. Normal distribution curve (bell shaped curve). The peak
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e mode. Distribution of deviations is uniform around the mean

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Normal distribution is usually not found in pharmaceutical powders because of uneven size
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reduction process. The distribution of particles in a powder is termed as unsymmetric or skewed,

i.e. uneven around the mean. If frequency curve is elongated towards higher size range, the
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pattern is known as positive skewness. If frequency curve is elongated towards lower size, the
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pattern is known as negative skewness. It is normally shows a long tail of larger particle size.
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n (rs Weight distribution 30
40

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Number distribution Weight distribution

30
30Numberdistribution
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l0
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10
10
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40
20 30
510 15
20 25 30 35
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40
log particle size (um) Data ae
Particle size (um)
Figure 6-3. Normal distribution uurve for a powder. Data ae 64 Log-normal distribution curve for a
from Table 6-2. Distribution of particles is re3 and
or less
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takenfrom Table 6-1. Uneven distribution around the mean. Lorg nd the mean (x axis: column 2; y axis: colu
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tail of larger particles (x axis.column 2,y axis: columns 4 and 5

Log-normal distribution curve:

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In this type, frequency on y axis is plotted against log mean particle size on x axis. Advantage of
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this curve is that the distribution pattern is made symmetrical. When compared to normal
distribution curve. Powders obtained by crystallization and milling methods exhibit log-normal
distribution. Powder blend obtained from granulation may have different type of distribution.
Cumulative frequency distribution curve:
In this plot, cumulative percentage over size (or under size) is drawn against particle size. If
summation of frequencies is carried out from the bottom upward, the result expressed as the
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percentage particle over size. Summation downwards gives percentage undersize. Data yield a
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sigmoid curve with the mode, i.e. particle size at the greatest slope. The advantage of this plot is
that one can directly read the percentage within any given size range without any difficulty. The
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disadvantage is that scattering of points cannot be identified.
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120
Number distribution
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100
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80
60 weight distribution
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20 30
Particle size (um)
Figure 6-5. Cumulative frequency
taken from
distribution
Table 6-2 (x axis: column 1: y axis:
curve.
columns
Data
4 and
ar 6)
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Log-Probability plot:

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A plot is drawn by taking log particle size on x axis and cumulative percent frequency of the
probability scale on y axis. In this plot, the cumulative curve is converted into a straight line. A
straight line is completely defined by one point and the slope. For the number distribution, slope
gives geometric standard deviation og. The reference point gives geometric mean diameter, dg.
which is equal to the median or the diameter at 50% on probability scale.
Probability plot is necessary when certain data points are not well defined. For example,
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in the sieve analysis, how much material has passed through the top sieve is known. For this data
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point, we have to identify the midpoint interval of the top, which is not known.
The advantages of probability graph are:
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1. Error of data points are averages by taking a best fit line.
2. Linearity or lack of linearity can be identified.
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Number distribution
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Weight distribution

10
50%
SIZe
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16% 16% undersize
under size
30
=8.511 = 12. .58
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8.51
50
1.48
70
90

99

99.9
dg 12.58 um dg 19.95 umm
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0.5 O.8 1.2

1.0
Particle size (um) log scale
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gure 6-6. Log probability plot. Data in Tade
2: y
Xaxis: column axis: columns 4 an
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Particle size determination-Methods:
Many methods available for determining particle size such as optical microscopy, sieving,
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sedimentation and particle volume measurement.

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1. Optical microscopy (range: 0.2-100 um).

2. Sieving (range: 40-9500 um).
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3. Sedimentation (range: 0.08-300 um).

4. Particle volume measurement or conductivity method (range: 0.5-300 um).
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1. Optical microscopy:
The optical microscopy can be used to measure the particles size in the range of 0.2 um to about
100 um. In this method the size is expressed as dp projected diameter. By this method the
number distribution data can be obtained and it can be converted to weight distribution. The
a

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resolving power of optical microscope is less as compared to ultramicroscope or electron
microscope. In this method, an emulsion or suspension, diluted or undiluted, is mounted on a
slide or ruled cell. Eye-piece of the microscope is fitted with a micrometer, called ocular
micrometer. The eyepiece or ocular micrometer is calibrated using a stage micrometer. The slide
or ruled cell is placed on a mechanical stage. The size of particle is determined with the help of
ocular micrometer. The field can be projected onto a screen where particles are measured more
accuratly and photograph can be taken. The optical microscopy method can be used to determine
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the particle size analysis in suspensions, in aerosols or in emulsion (droplet size). In order to get
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statistically valid results the counting of particles should be in the range of 500 to 1000 particles
for every sample.
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From the obtained data the size frequency distribution curves, cumulative frequency
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curves are plotted. Other popular measurements includes Feret diameter, the Marti diameter
-
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and projected area diameter.
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Length
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Feret's diometer
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Martin's diameter
Projected area diometer
Maximum horizontal intercept
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Popular measurements:
Feret's Diameter-The distance between imaginary parallel lines tangent to a randomly
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oriented particle and perpendicular to the ocular scale.
Martin's Diameter-The diameter of the particle at the point that divides a randomly oriented
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particle into two equal projected areas.
Projected Area Diameter- The diameter of a circle that has the same projected area as the
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particle.
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LengthThe longest dimension from edge to edge of a particle oriented parallel to the ocular
Scale.
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Width-The longest dimension of the particle measured at right angles to the length
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Advantages
1. Microscopy method allows the direct observation (shape and size) of particles
2. The field can be projected and a photograph can be taken.
3. Aggregation of particles can be easily detected.
4. Provides accurate results and reproduciability.
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5. Simple and economic.

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6. Easy to handle.
Disadvantages
1. Diameter is obtained from only two dimensions of the particle i.e., length and breadth. No

estimation of depth (thickness) of particle.

2. The method is slow and tedious, because the number of particles that must be counted (300-
500) to obtain a good estimation of the distribution.
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3. Time consuming method.
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4. Large sample is required.
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2. Sieving method:
Particles having size range between 40 to 9500um are estimated by sieving method. In
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this method, the size is expressed as dsieve, which describes the diameter of a sphere that
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passes through the sieve aperture as the asymmetric particle. This method directly gives
weight distribution. This method is also known as analytical sieving.
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The sieving method finds application in dosage form development of tablet and capsules.
Normally 15% of fine powder should be present in granulated mass to get as proper flow and
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achieve good compaction in tabletting. Therefore, percent of coarse or fine powder can be
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quickly estimated. In addition, sieving also separated the powder can be quickly estimated. In
addition, sieving also separates the powder into fractions of desired size.
Sieves for pharmaceutical testing are considered from wire cloth with square meshes,
woven from wire of brass, bronze, stainless steel or any other suitable material. Sieves should not
be coated or plated. There must be no reaction between the material of construction of the sieve
and the substance to be sieved.
a

Method:
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Standard sieves of different mesh numbers are available commercially as per the
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specification of IP and USP. Sieves are arranges in a nest with the coarsest at the top. A sample
of the powder is places on the top sieve. This sieves set is placed in the mechanical shaker
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lP
apparatus and shaken for a certain period of time. The powder retained on each sieve is weighed.
Frequently, the powder is assigned the mesh number of the screen through which it is passed or
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on which it is retained. It is expressed in terms of arithmetic or geometric mean of the two

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sieves. Data are analyzed for normal, log-normal, cumulative percent frequency distribution and
probability curves. The relevant diameter such as geometric mean weight diameter and standard
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deviation can be obtained.

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C

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Advantages
1. It is simple for handling.
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2. It is inexpensive and rapid.
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3. Provides reproducible results.
. Specially useful for weight distribution.
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5. It can be used for very small particles having particle diameter upto 5J.Im.
Disadvantages
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1. It cannot used for very small particles is below 5J/m.
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2. The powder sample should be dried every time, otherwise it may clog with particles, resulting
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improper sieving
3. During shaking, attrition of particles may cause reduction of particle size. This may leads to
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errors in estimation.
4. Time consuming method.
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5. Approximate results can be obtained.

3. Sedimentation method:
The sedimentation method can be used for formulation and evaluation of suspensions.
emulsions and determination of molecular weight of polymers. The particle size in the subsieve
range may be obtained by gravity sedimentation and is expressed as stokes' diameter, dst' in
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Stokes' law.
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18ph
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Ve-P)8
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lP

lP
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Where,
dt= Stokes diameter of the particle
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= viscosity of the medium

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h = height of fall in time

Ps = density of the particles
Pl= density of the medium
g acceleration due to gravity
t= time interval
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The apparatus usually consists of 550ml vessel containing a 10ml pipette sealed into a

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ground glass stopper. When the pipette is in place in the cylinder, its lower tip is 20cm below the
surface of the suspension.
The procedure is as follows:
and to that add suitable
I or 2% suspension of powder in a suitable medium firstly prepared
deflocculating agent. Transfer this mixture (suspension) into the Andreasen vessel. Place the
stopper and shake the vessel to distribute the particles uniformly throughout the suspension and
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the apparatus is place in a constant temperature bath. Remove the stopper and attach tw0-way
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stopcock. At various time intervals, 10ml samples are withdrawn and discharged by means of the
two way stopcock. The samples are evaporated and weighed or analyzed by any method,
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correcting for the deflocculating agent that has been added. The weight or the amount of particles
obtained in each time interval is referred to as weight undersize. The weights are converted into
lP

lP

lP
cumulative weight undersize.
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Suction tofill
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pipette to 10 ml
mark
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TWO way
stopcock for
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draining
sample Ground-glass
Joint

Pipette tube Scale

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lP

lP

lP
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4. Particle volume measurement or conductivity method:

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The popular instrument to measure the volume of particles is the coulter counter. This
method gives number distribution. Here the particle volume is measured and is converted into
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particle diameter, and size is expressed as volume diameter dv. The method is useful in the study
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of particle growth in suspension and solutions, useful in dissolution studies and to study the
effect of antibacterial agents on the growth of microorganisms. This method gives quick and
accurate results.

The working principle of coulter counter is that when a particle suspended in a liquid
containing electrolyte (sodium chloride) passed through a small orifice, and maintains contact
a

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with the external medium. Generally, a known volume of a dilute suspension is pumped through

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the orifice. The suspension is sufficiently diluted so that only one particle can pass at a time
through an orifice. A constant voltage is applied across the two electrodes. Here the current
produces. When a suspended particle travels through the orifice, it displaces its own volume of
electrolyte. The resistance, between two electrodes increases. The net result is a change in the
electrical resistance, which is related to the particle volume, causes a voltage pulse. The voltage
pulse are amplified and fed to a pulse height analyzer calibrated in terms of particle size.
a

a
The pulses are electronically counted for a given threshold value. By adjusting the
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threshold setting the number of particles of each size range is obtained. Thus the particle size
distribution can be obtained.
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The instrument is capable of counting particles at the rate of approximately 4000 per second. The
data may be converted from a volume distribution to a weight distribution.
lP

lP

lP
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|Electrolyte Main Threshold Pulse
solution amplifier Circuit ampliier
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Mercury
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2Electrolyte
solution
and Pulse height
proportional to .
L Scope
particles particle volume
Counter
drive
UWorifice Digital

Loo L register
a

Counter switch
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Coulter counter apparatus

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Advantages
1. It gives very fast results [approximately 4000 particles per second].
lP

lP

lP
2. Short period of time is required for size distribution analysis.
3. It provides accurate results.
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4. It can be used to measure particulate contamination in parenteral solutions.

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5. Submicron particle sizing instrument, the coulter Model N4 has been developed for analyzing
particles in the range of 0.003 to 0.3 um.
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6. It is used in the study of the clustering process and the packing of the mineral components of
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renal stones.
7. It is also useful in quality control of large volume parenteral [LVP] solutions.
Disadvantages
1. It is not suitable for polar and highly water soluble materials due to solvation.
2. It is expensive method.
Specific surface:
a

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Specific surface is defined as the surface are per unit weight (Sw) or unit volume (Sv) of the

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material.

Determination of surface area:

The commonly used methods are:
1. Adsorption method
2. Air permeability method
a

a
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Specific Surface
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Surface area of particles
S Volume of particles
lP

lP

lP
number of particles x Surface area of each particle
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number of particles x Volume of each particle
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na,d d3
nayds ayd
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Surface area Surface area
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Sw = Weight Densityx Volume

S a,dýs
S na,dys xp

ay dys P
a

above
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When the particles are spherical, equation simplifies to

6
S
ha

ha

ha
pdys

s
lP

lP

lP
Since 6.0 for a sphere.
Adsorption method:
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Principle: A large specific surface allows good adsorption of gas and/or solutes from a solution.
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The volume of gas (in m) adsorbed per gram of adsorbent (solid) can be plotted against the
pressure of gas introduced at constant temperature. At low pressure, the gas adsorbs on the
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surface of adsorbent and form a monolayer. At saturation, the amount of adsorbed is a function
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of surface area of powder. At high pressure, the adsorbed layer becomes multi-molecular. The
completion of mono-molecular film can be identified using BET equation. At that stage, the
volume (ym) adsorbed per one gram can be obtained.
a

a
rm

rm

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C

C
P
(b-p P
yPo -
P) ymb (18)
Ymb Po
where p = pressure of the adsorbate,
volume of vapor (gas) per mmHg
gram, g
Po vapor pressure at
saturation(monolayer), mmig
amount of vapor adsorbed per
unit mass of adsorbent,
when the surface is
a

a
= constant, covered with monomolecular layer, g
b proportional to heat of adsorption and latent
rm

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of condensation
of subsequent layers hea
When, p/po =
1, the vapor pressure p
ha

ha

ha
is equal to saturation vapor
pressure. Quinsorb QS-16 is used for obtaining the data needed to
calculate the surface area.
lP

lP

lP
20
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15
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10
ar

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-

B
C

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5

O 0.2 0.4 0.6 0.8 1.0

p/Po

Fig. 6-12 Adsorption isotherm showing the volume of nitro-

gen gas absorbed on the powder. The first inflection point,
a

B, represents the completion of monomolecular layer (ym).

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Procedure A known weight of powder is introduced into the

:
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ha
sample tube. The sample is mounted to the out-gassing station toAA
remove gas. Then the sample tube is mounted to the analysis station. gas
lP

lP

gas. Nitrogen
lP
mixture of helium and nitrogen are used as adsorbate (inert). Vapour
adsorb
adsorbs on the powder and helium does not
el

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A mixture of gases is
dosing options are available with the instrument. at a specific pressure
passed through sample tube (containing powder)
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and temperature (thermostat facility). The amount of nitrogen gas

a thermal conductivity detec-
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adsorbed and desorbed is measured usiig to the rate of adsorption or

tor. The signal height is proportional
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the curve is proportional to

desorption of nitrogen gas. The arez under at several
The adsorption is measured,
ne gas adsorbed on the particles.
a

a
rm

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pressures, so that BET equation plot can be obtained. Gaussian o Deu

shaped curve is plotted on a strip chart recorder.

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Advantages : Quintasorb is versatile in the sense that it pemits the
use of a number of gases (or gas mixtures) over a range of temperatures.
It allows the evaluation ot characteristics of porous material. In addition,
it can be used to measure true density of the powder, pore size and pre-
volume distribution. These can be used for studying physisorption and
chemisorption. It is applicable to a wide range of surface arcas.
a

a
Air Permeability Method - Fisher-Subsieve Sizer
rm

rm
Air permeability method is offical in IP. This method also used to
estimate surface diameter. d
ha

ha

ha
Principle : Powder is packed in the sample holder as a compact plug.
lP

lP

lP
In this packing. surface-surface contacts between particles appear as a
series of capillaries. The surface of these capillaries is a function of the
el

el
surface area of the powder. When air is allowed to pass, air travel
through these capillaries and thus this method is related to surface area
ew

ew
of powder. When air is allowed to pass at a constant pressure, the bed
resists the flow of air. This results in a pressure drop. The greater the
ar

ar
surface area per gram of the powder, S, the greater the resistance to
C

C
flow. The permeability of air for a given pressure drop is inversely
proportional to specific surface.
The Kozeny-Carman equation is used to estimate the surface area by
this method. This is based on the principle of Poiseulle's equation.
4Pt
V ..(19)
KI (I-E)
a

a
rm

rm

where A = cross sectional area of the bed (pack), m*

AP pressure difference of the plug, Pa (or mmHg)
ha

ha

ha
! = time of flow, s

I = length of the sample holder, m

lP

lP

lP
E = porosity of the powder
el

el

S = surface area per gram of the powder, m/g

ew

ew

h = viscosity of the air Pa.s

K = a constant (5.0+0.5) that accounts the irregular capillaries
ar

ar

V = volume of air flowing through the bed, m°

C

Poiseulle's equation is same as that used in Ostwald's viscometer,

the principle of flow of liquids through the capillary tube. Fisher
subsieve sizer instrument is commercially available.
a

a
rm

rm

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ar
Method: Assenbling of the apparatus is shown
in Figure 6-13. It

C
consists of a sample tube containing the packed
end connected tO an au pump through a
powder sample with one
constant pressure regulator.
The other end is altached to a calibrated
manometer containing a suit-
able liquid of lov VIsCOsity and negligible
vapor pressure.
The air pump builds up air pressure and
is connected to a constant
pressure regulator. Air is passed through the dryer
to remove any
moisture. Air is then allowed to flow through the
a

a
packed powder in the
sample tube. The flow of air is measured by
rm

rm
the manometer. The level
of the fluid in the manometer is related to the average
diameter of the
particles. The higher the surface area, the greater is
ha

ha

ha
the resistance, the
pressure drop is higher and manometer level
decreases. Commercial
equipment is standardized to eliminate the mathematical
lP

lP

lP
computation.
Average particle diameter can be read from the calculator
charts sup-
plied with the equipment.
el

el
ew

ew
The porosity of the powder (E) and viscosity of air (7) are estimated
separately. A and l are constants represent sample holder. AP and V can
ar

ar
be obtained from the experiment and substituted in equation (19) in
order to estimate the surface area.
C

C
Calibrating
From air pump
valves

E Porous
plugs
a

a
rm

rm

Powder Pressure
ha

ha

ha
sample varies
Constant with
lP

lP

particle
lP
pressure
SIze
regulator

J
el

el
Dryer
Manometer
ew

ew

TTTD
ar

ar
C

Fig. 6-13 The Fisher subsieve sizer.

If the powder has decreased porosity, the dys also decreases. There-
Iore, over a range of porosities, the minimum value of diameter
is
achieved.
a

a
rm

rm

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C

C
Advantages

1. Simple instrumentation and high speed, it is widely used pharmaceutically for specific
surface determinations.
2. Bephenium hydroxynaphthoate, official in the B.P.C., 1973 is standardized by air
a

a
permeability method.
rm

rm
3. Activity of some drugs is related to the specific surface. Ex: Anthelmintic drugs in
suspension dosage form must possess a surface area of not less than 7000 cm/g. As the
ha

ha

ha
specific surface of the material is reduced, the activity of the drug also falls.
4 Air permeability method, officially in U.S. pharmacopoeia used for determining the specific
lP

lP

lP
surface area of griseofulvin.
5. This method is also used for measuring the fineness of Portland cement.
el

el
ew

ew
Derived properties of powders:
True density: it is the density of the material itself. It is defined as:
ar

ar
rue density, pp
weight of powder
True Pp== true volume
C

C
of powder
The density is dependent on the type of atoms in a molecule, arrangement of the atoms in
a molecule and the arrangement of molecules in the sample. Apart from true density, powder is
also characterized by granule density and bulk density.
Volume occupied by voids and intraparticle pores are not included in true density. The
most common methods used in the determination of the true density are gas (helium or nitrogen)
displacement, liquid displacement and flotation in a liquid. Helium and nitrogen gases obey the
a

a
rm

rm

ideal gas law at ambient temperatures and pressures. However, helium is preferred because of its
smaller size. Both gases do not adsorb on the material.
ha

ha

ha
lP

lP

lP
el

el
ew

ew
ar

ar
C

C
a

a
rm

rm

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ar
248

C
spaces
(inter-particle and intraparticle
Volume occupied by voids The true densities
pores are not included in true density
(Figure 6-15).
in Table67
some pharmaceutically important powders are Iisted
of
true
common methods used in the determination of the
The most displacement, liquid displacement
density are gas (helium or nitrogen)
the ideal ga
flotation a liquid. Helium and nitrogen gases obey
a

a
and in pre
and pressures. However, helum is
rm

rm
law at ambient temperatures
its smaller size. Both gases do not adsorb on the
ferred because of
ha

ha

ha
matenal.
Helium penetrates
Porous solids-Helium displacement method:
lP

lP

lP
the smallest pores and crevices.
method
Therefore, this a value gives

closer to its true density. This is a valuable

tool to estimate the true
el

el
density, particularly for porous solids.
ew

ew
pycnometer is
Method: The schematic representation of helium
which can be
ar

ar
shown in Figure 6-16. It consists of a sample holder (A),
sealed after placing the sample. The valve (B) is connected to
the
C

C
the sample
sample holder. It has provisions for removing the air from
holder and introducing the helium gas. Helium gas is selected as does
it

is included in
not adsorb on the solid sample. A pressure detector (C)
order to maintain preset constant pressure. It has sealed bellows which
maintains the electric contact at a particular pressure. A piston (D) is
attached in order to read the coresponding pressure, which is also
a

a
rm

rm

related to the volume of the powder.

ha

ha

ha
Hetium
lP

lP

lP
(6)
Atmos Valve Vacuum Electrical
el

el

contact
ew

ew

.
ar

ar
C

(o) Sample (c)Pressure

cell
detector
"U
(d) Variable
volume
piston
a

a
rm

rm

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C

C
Initially. the volume of eapty pyenorneter is determined The air
oresent in the sample holder is removed by applying vacrun Then
thelium gas is passed nto the apparatus through the valve (B). The
oressure is adjusted and set a particular valure with the heip of a movable
niston (D). At this position, the reading on the scale denotes U. This
represents the volume of empty cell.
In the next step, Pycnometer is calibrated by placing a standard
sample of known true volume (V) (stainless steel spheres) in the sample
a

a
is removed. The sarne
holder The sample holder is sealed and air
rm

rm
amount (as used in the first step) of the helium gas is introduced.
Pressure is adjusted to preset valuc by moving The piston
the suitably. At
ha

ha

ha
difference between
this stage, the scale reading is denoted by Ua. sphere.
UI and U2 gives the volume occupied by the
lP

lP

lP
sample.
The last step involves the determination of volume of the The air
sample powder.
The stainless steel sphere is replaced by the test(same quantity as used in
el

el
gas
in the pycnometer is replaced by helium
ew

ew
piston. At this
earlier steps). The pressure is adjusted with the help of between U
state, the piston reading is denoted by U The difference
ar

ar
and U, gives the volume occupied by the sample.
C

C
is:
The operating cquation for the instrument
V (21)
V,U-U2(U-U,1
where V, true volume of the sample, cm'.
=

True volume and weight of the sample are substituted in equation

(20) gives the true density
a

such as water and ethyl

rm

rm

Liquid displacement method :Liquids

is nonpo-
alcohol cannot occupy the pores and crevices. If the powder powder is
ha

ha

ha
rous, this method is used. Select a solvent in which the
insoiuble and heavy. Normally. the values obtained are somewhat lower
lP

lP

lP
hanthe helium displacement method.
Method: Pycnometer or specific gravity bottle may be used.
el

el
ew

ew

Weight of pycnometer = W1
Weight of pycnometer+ sample (or glass beads) = W2
ar

ar

Weight of sample= W3 = W2 w1
C

Weight of pycnometer with powder and filled with solvent= w4

of
Weight of the liquid displaced by solids (related to volume
iiquid displaced)= W4 W2
a

a
rm

rm

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ar
True density = Ww1

C
w4-w2
Compressed powders: The powder sample is compressed into a tablet using a punching
machine with 1,00,000 Ib/sqin. Now estimate the true density.
Weight of the tablet = WI
Volume of the tablet = V
w1
True density
Granule density: Granule density is determined for the granules that are employed in the
a

a
rm

rm
manufacture of tablet.
Granule density is defined as:
ha

ha

ha
Granule density
Granule density, P9 Granule
volume
lP

lP

lP
The volume of granules can be measured by mercury displacement method. Mercuryis
el

el
suitable because it fills the voids, but fails to penetrate the internal pores of the particles. The use
of mercury is also based on its high contact angle of about 140" and its nonwetting
ew

ew
characteristics.
ar

ar
Bulk density: It is defined as:
mass of a powder (w)
Bulk density (p) =
C

C
bulk volume (Vb)
When particles are packed loosely, lots of gaps between particles are observed. Hence bulk
volume increases making the powder light. Based on bulk volume, powders are classified as
"light" and "heavy". Light powders have high volume
Tapped volume: The powder is passed through a standard sieve no. 20. The weighed powder
(100gm) is transferred into a 250ml measuring eylinder. The level of powder is made without
compacting. The unsettled apparent volume is measured (Vo) to the nearest graduated unit. The
a

a
rm

rm

cylinder is fixed on the bulk density apparatus and the timer knob is set for 100 tapping. The
eylinder is tapped and volume readings are taken until little further volume change is observed.
ha

ha

ha
mass of a powder (m)
Tapped density
volume of the powder bed at zero tapping (V0)
lP

lP

lP
el

el
ew

ew

Applications:
1. Bulk density is used to check the uniformity of bulk chemicals.
ar

ar

2. The size of the capsule is mainly determined by bulk volume for a given dose of material.
The higher the bulk volume, lower will be bulk density and bigger the size of the capsule.
C

weight of formulation
Capsule volume = CUPSule JUl
tapped bulk density
3. It helps in selecting the proper size of a container, packing material, mixing apparatus in
the production of tablets and capsules. The capacity of a mixing bowl is usually
expressed in cubic feet or liter. Normally, the volume of formulation and an excess of
10% of the volume is considered for the selection of container for the mixing process.
a

a
rm

rm

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ar
of batch
Capacity of mixing bowl = Weght

C
bulk volume
Porosity:
True volume = Volume of the powder itself.
Granule volume = Volume of the powder itself + volume of interparticle spaces.
Bulk volume = Volume of the powder itself + volume of interparticle spaces + volume of inter-
particles spaces (voids)
if the powder is nonporous i.e. no internal pores or capillary spaces, the bulk volume consists of
a

a
true volume plus the volume of spaces between the particles, i.e. void volume,
rm

rm
Void volume = V= bulk volume true volume or Vb- Vp
-

The porosity or solids, e, of the powder is defined as:

ha

ha

ha
Porosity or voids e void volume
lP

lP

lP
bulk volume
bulk volume true volume
-
Vb-Vp
bulk volume Vb
el

el
Porosity is frequently expressed in per cent.
ew

ew
= X
Percent, e 1- 100
Vb
ar

ar
The above equation can also be expressed in terms of density values.
Percent, E = X100
C

C
pb
Applications:
Certain powders contribute immensely to the porosity of the tablet. Porosity influences the rate
of disintegration and dissolution. The higher the porosity. the faster the rate of dissolution. Based
on porosity values, solids can be classified as porous and nonporous. Porosity is applied in the
studies on adsorption and diffusion of drug materials.
a

FLOW PROPERTIES:
rm

rm

Flowability is the ability of a powder to flow through reliably. Flow properties influence
mixing and de-mixing of powders. These also influence the design of formulation and selection
ha

ha

ha
of process equipment.
Angle of repose:
lP

lP

lP
The flow characteristics are measured by angle of repose. Improper flow of powder is due to
frictional forces between the particles. These frietional forces are quantified by angle of repose.
el

el

Angle of repose is defined as the maximum angle possible between the surface of a pile of the
ew

ew

powder and the horizontal plane.

By definition
ar

ar

tan =
C

0 tan-1
Where h= height of pile, cm
r= radius of the base of the pile, cm
angle of repose.
a

a
rm

rm

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The lower the angle of repose, the better the flow property. Rough and irregular surface of

C
particles gives higher angle of repose.
Procedure: A glass funnel is held in place with a clamp on a ring support over a glass plate. The
glass plate is placed on a micro-lab jack. Approximately 100 gm of powder is transferred into the
funnel keeping the orifice of the funnel blocked by the thumb. As the thumb is removed, the lab-
jack is adjusted to lower the plate and maintain about 6.4 mm gap between the bottom of the
funnel stem and the top of the powder pile. When the powder is emptied from the funnel, the
a

a
angle of the heap to the horizontal plane is measured with a protractor.
rm

rm
The height of the pile (h) and the radius of the base (r) is measured with the ruler. The
angle of repose is this estimated. Cohesive powders yield better results if measurements are
ha

ha

ha
carried out using a funnel with a 30 mm stem opening.
lP

lP

lP
el

el
Scale of flowability
Flow property
ew

ew
Angle of repose
25-30 Excellent
ar

ar
31-35 Good
36-40 Fair, aid is not needed
C

C
41-45 Passable, may hang up
46-55 Poor, must agitate or vibrate
56-65 Very poor
66 Very very poor
a

ANGULAR TESTS: Angular tests are applicable to relatively free flowing powders containing
rm

rm

particles larger than 100 um. such powders cannot be investigated satisfactory using shear cells
and tensile strength apparatus.
ha

ha

ha
If granulation is tested for flow, then flow meter is the method of choice.
If known forces are utilized during the flow, shear cell is a method of choice.
lP

lP

lP
These are strictly empirical between the degree of compaction and powder flow. Based on
experimental variables, one of the following can be used.
el

el

Height of funnel is fixed, but the height of powder varies, as the pile is formed.
ew

ew

Base diameter is fixed or diameter is fixed or diameter of powder cone may be allowed to
change, as the pile is formed.
ar

ar

Angular properties of powders also depend on the details of the measurement. Angle of
C

repose is not an intrinsic property of a powder and is primarily a function of surface roughness.
Angle of repose provides qualitative information.
Rough and irregular surface of particles give higher angle of repose.
Cohesive particles tend to form higher heaps, which cannot spread out. Angle of repose
of such powders will be higher or poor flow.
a

a
rm

rm

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Drained angle: It is the angle observed, when powder flows from a conical surface onto a flat

C
bottomed container, if the powder is discharged through the orifice in the base. The drained
angle is affected by the degree of consolidation of the material in the hopper. Method- wise it is
like angle of repose.

Poured angle: The poured angle of repose can be measured, when the powder is allowed to pour
onto the flat surface. The angle is measured from the height of the heap. A protector is
a

a
commonly used for measurement. In this case, the word conical surface was not mentioned. For
rm

rm
the some powder, drained angle is larger than the poured angle. In case of poured angle, the
particles slide and roll down from the powder surface. In case of drained angle, convergence
ha

ha

ha
occurs, i.e. particles get mixed up with the remaining pile and nesting in the container.
Dispersibility: Dispersibility of a powder is the ability of a material to flow or pour easily over a
lP

lP

lP
plane. Dispersibility, dustiness and flow ability are inter-related terms.
Method: Weigh approximately 10 gm of the sample. The material is dropped enmasse from a
el

el
total weight on to a tarred watch glass through a hollow cylinder placed vertically 102 nmm above
ew

ew
the watch glass. The cylinder is secured to a support stand by 102 mm diameter support rings
placed above and below the cylinder. The drop point is approximately 178 mm vertically above
ar

ar
the top of the cylinder. The material landing within the watch glass is weighed. Any loss of
C

C
powder during the fall is the result of dispersion. The percent Dispersibility is calculated using
the relationship.
weight of powder n watcn glass y 100
Dispersibility (%) =
initial weight of the sample
Carr's index: It is defined as:
density
Consolidated index tapped density-fhuff x 100
tapped density
a

This property is known as compressibility. It is indirectly related to the relative flow rate,
rm

rm

cohesiveness, particle size, shape and moisture content. It is simple, fast and popular method of
predicting powder flow characteristics.
ha

ha

ha
Fluff density is the ratio of mass of powder to the fluff volume. Fluff volume is the
volume occupied by a certain mass, when gently poured into a measuring cylinder. This is
lP

lP

lP
known as aerated density.
Tapped density is the ratio of mass of powder to the tapped volume. Tapped volume is
el

el

the volume occupied by the same mass of powder after a standard tapping of a measure.
ew

ew

Compressibility index can be a measure of the potential strength that a powder could build up in
its arch in a hopper and the ease with which such an arch could be broken. It is a simple and fast
ar

ar

method.
C

Method: using a suitable adhesive, the base of a 10 ml. tarred measuring cylinder is fixed to the
standard rubber bung at the top of the 250 ml eylinder. A powder sample is transferred into the
tarred 10 ml eylinder with the help of a funnel. The 250 ml measuring cylinder is placed on the
tapping apparatus. The initial volume occupied by the powder is denoted as Vo.
The contents are tapped in the following order., 2,4,6,8,10,20,30 and 50 taps. After
completing the tapping, the volume is denoted as V2, Va..V50
a

a
rm

rm

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The powder is carefully collected from the cylinder and weighed (W).
n g/cm3

C
Fluff density (pb, minimum) =
W
Tapped density (pb, maximum) = vn 9/cm3
Hausner ratio: It is defined as:
Hausner ratio = Vo
Vr
a

a
Where Vo = volume of the powder bed at initial stage, ml
rm

rm
Vi= volume of the powder bed after tapping, ml
Hausner ratio is related to the morphological behavior. For example, flow properties
ha

ha

ha
increasing sphericity. The Vr means repeated taps or as needed, until the difference between the
lP

lP

lP
successive measurements is less than 2%.
el

el
Particle Number: The particle number is important in dose of drugs specially for potent drugs
ew

ew
or drugs having low dose. Knowledge of particle number is important in preparation of tablets
and capsules. The number of particles per unit weight, N, is expressed in terms of volume
ar

ar
number mean diameter, dvn. Assuming that the particles are spheres, the volume of a single
ivn
gram per particle. The number of
C

C
particle is and the mass (volume x density) is
6
particles per gram may be obtained from following relationship.

(Tdn 6g =
N
Particle
So, N= 6
a

vnp
rm

rm

Ttd
ha

ha

ha
lP

lP

lP
el

el
ew

ew
ar

ar
C

C
a

a
rm

rm

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