Micromeritics

Manas Bhowmik
 Introduction

The science and technology of small particle is termed as micromeritics by JM Dalla

Valle. It is the study of the fundamental and derived properties of the individual as well
as collection of particles. The knowledge and control of the size of the particles is of
important in pharmacy.
 Importance of micromeritics

Importance:
1. Size, size range, and hence surface area of particle of a drug inference its physical, chemical
and pharmacological properties.
2. Particle size affects the release of the drug from its dosage forms.
3. The formulation, physical stability and therapeutic response of suspension, emulsion and
tablet dosage form depend on the particle size achieved in the product.
4. In the area of tablet and capsule manufacturing, control of the particle size is essential in
achieving the necessary flow properties and proper mixing of granules and powders.
 Importance of micromeritics

Before eliciting any therapeutic response, drug should enter into the systemic circulation
across the lipid bilayer of the GIT, and mostly unionised drug in the form of solution can cross
the lipid bilayer by simple diffusion and ionized forms are absorbed by carrier mediated
mechanism. So it implies that, before absorption, drug should undergo solubilisation because
most of the drugs are solid in nature (exception- Trinitroglycerine which is a liquid).
 Importance of micromeritics

 Particle size is related to the solubility and dissolution of the drug. When particle size is
reduced by any means, new surface is produced by disruption of the intermolecular bonds
that generates surface energy (J/m2) which is the excess energy at the surface as compared
to the bulk.
 It is clear that reduction in particle size resulted in increase in surface area.
 When surface area is increased, surface free energy is also increased according to Gibbs
theory ∆𝐺 = 𝛾𝑆𝐴 . ∆𝐴 the equations it is observed that reduction of particle size results in
increase in surface free energy.
 Importance of micromeritics

 Thermodynamically, the free energy changes involved in the different stages of wetting are
∆𝐺𝐴 = 𝛾𝑆/𝐿 − 𝛾𝑆/𝐴 − 𝛾𝐿/𝐴 for adhesional wetting, Thermodynamically, the tri-phasic
equilibrium can be expressed by Young's equation: 𝛾𝑆/𝐴 = 𝛾𝑆/𝐿 − 𝛾𝐿/𝐴 cos 𝜃 and the free
energies can be expressed in terms of contact angle i.e., ∆𝐺𝐴 = −𝛾𝐿/𝐴 1 + cos 𝜃 for
adhesional wetting,
 Therefore, when free energy is increased due to size reduction of the particle, contact angle
is reduced and the liquid adhere to the solid surface following immersion and spreading
throughout the liquid thereby increase in dissolution.
 Importance of micromeritics

 Particles of colloidal dispersions are to small and visualized by ordinary microscope whereas
very fines are visualized by optical microscopy. Large particles or granules are fall under the
sieve range. The unit of the particle size in micrometrics is micron (µ).
 µ = 10−6 m = 10−4 cm = 10−3 mm
 nm = mµ = 10−9 m
 Particle size and size distribution

In a collection of particles of more than one size, two properties are important:
i) shape and surface area of the individual particles
ii) size range and number of particles or weight.

The size of a spherical particle is expressed in its diameter. As a degree of asymmetry of the
particle increases, expression of size in a meaningful diameter is difficult. In such situation no
one unique diameter is there and an equivalent spherical diameter must be made which can
relate the size of the particle to the diameter of a sphere having same surface area, volume or
diameter.
 Diameters

a. Surface diameter (𝑑𝑠 ) =it is the diameter of a sphere having the same surface area as the
particle in question.
b. Volume diameter (𝑑𝑣 ) = It is the diameter a sphere having the same volume as the particle.
c. Projected diameter (𝑑𝑝 ) =It is the diameter of a sphere having the same observed area as
the particle when viewed normal to its most stable plane.
d. Stokes diameter ( 𝑑𝑠𝑡 ) = It is the diameter of an equivalent sphere undergoing
sedimentation at the same rate as the asymmetric particle.
 Particle size and size distribution

In a collection of particles, it is important to know not only the size of particles, but also the
number of particles having same size is important too. The particle size distribution is
essential where estimation of size range and the corresponding numbers or weight fractions
are needed for calculation of average particle size for a sample.
 Average particle size

σ 𝑛𝑑 𝑝+𝑓 1ൗ
Edmundson’s derived equation 𝑑𝑚𝑒𝑎𝑛 = ( σ 𝑓 ) 𝑝
𝑛𝑑

n is the number of particle in a size range having mean size range or diameter d. p is the index
related to the size of particles. p= 1, 2 or 3 represents the length, surface or volume respectively.
The frequency with which a particle occurs in a certain size range is expressed as 𝑛𝑑 𝑓 where f is the
frequency index and f= 0, 1, 2 and 3 correspond to number, length, surface and volume respectively.
Calculation of statistical diameter from data obtained from microscopic (Normal distribution)

Table: 1
Size range Mean size Number of
(µm) range d particles in each 2 3 4
(µm) size range (n)
𝑛𝑑 𝑛𝑑 𝑛𝑑 𝑛𝑑

0.50-1.00 0.75 2 1.50 1.13 0.85 0.64

1.00-1.50 1.25 10 12.50 15.63 19.54 24.43
1.50-2.00 1.75 22 38.50 67.38 117.92 206.36
2.00-2.50 2.25 54 121.50 273.38 615.11 1384.00
2.50-3.00 2.75 17 46.75 128.56 353.54 972.24
3.00-3.50 3.25 8 26.00 84.50 274.63 892.55
3.50-4.00 3.75 5 18.75 70.31 263.66 988.73

෍ 𝑛 = 118 ෍ 𝑛𝑑 = 265.50 ෍ 𝑛𝑑 2 ෍ 𝑛𝑑 3 ෍ 𝑛𝑑 4

= 640.89 = 1645.25 = 4468.95

Calculation of statistical diameter from data obtained from microscopic (Normal distribution)

Table: 2
σ 𝑛𝑑 𝑝+𝑓 1ൗ Value for data in
( ) 𝑝 p f Type of mean Size parameter Frequency Mean diameter the above table
σ 𝑛𝑑 𝑓
(µm)
1 0 Arithmetic Length Number 2.25
σ 𝑛𝑑 𝑑𝑙𝑛
σ𝑛
2 0 Arithmetic Surface Number 2.33
σ 𝑛𝑑2 𝑑𝑠𝑛
σ𝑛
3 0 Arithmetic Volume Number 2.41
3 σ 𝑛𝑑 3 𝑑𝑣𝑛
σ𝑛
1 1 Arithmetic Length Length 2.41
σ 𝑛𝑑2 𝑑𝑠𝑙
σ 𝑛𝑑
1 2 Arithmetic Length Surface 2.57
σ 𝑛𝑑 3 𝑑𝑣𝑠
σ 𝑛𝑑 2
1 3 Arithmetic Length Weight 2.72
σ 𝑛𝑑 4 𝑑𝑤𝑚
σ 𝑛𝑑 3
 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, frequency
distribution curve is obtained. This plot
gives a visual distribution but average
diameter can’t be achieved. It is
possible to have same average
diameter of two samples with different
distribution.
Fig.: 1
 Particle size distribution: Number & weight

Fig.3: Frequency distribution plot Fig.4: Cumulative frequency plot Fig.5: Log-probability plots
(log-normal relation)
 Conversion of number distribution to weight distribution (Log-Normal distribution)

Size Mean of No. of Cumulative 3

Cumulative
𝑛𝑑
range size particles in % frequency 2 3 % % frequency
𝑛𝑑 𝑛𝑑
(µm) range d each size %n undersize 𝑛𝑑 (Wt.) undersize
(µm) range (n) (No.) (Wt.)
2-4 3 2 1 1 6 18 54 0.03 0.03
4-6 5 32 16 17 160 800 4000 2.31 2.34
6-8 7 64 32 49 448 3136 21952 12.65 14.99
8-10 9 48 24 73 432 3888 34992 20.16 35.15
10-12 11 30 15 88 330 3630 39930 23.01 58.16
12-14 13 14 7 95 182 2366 30758 17.72 75.88
14-16 15 6 3 98 90 1350 20250 11.67 87.55
16-18 17 3 1.5 99.5 51 867 14739 8.49 96.04
18-20 19 1 0.5 100 19 361 6859 3.95 99.99

෍ 𝑛 = 200
 Hatch-Choate equation

The distribution may be represented by number or weight distribution or conversion of

number to weight or vice versa. The distribution is expressed by log-normal curve or
using Hatch-Choate equation.
Table 3: Hatch-Choate Equations for computing statistical diameter from Number & Weight Distributions

Diameter (Mean) Number Distribution Weight Distribution

𝑑𝑙𝑛 𝑙𝑜𝑔 𝑑𝑙𝑛 = 𝑙𝑜𝑔 𝑑𝑔 + 1.151 𝑙𝑜𝑔² 𝜎𝑔 𝑙𝑜𝑔 𝑑𝑙𝑛 = 𝑙𝑜𝑔 𝑑′𝑔 − 5.757 𝑙𝑜𝑔² 𝜎𝑔

𝑑𝑠𝑛 𝑙𝑜𝑔 𝑑𝑠𝑛 = 𝑙𝑜𝑔 𝑑𝑔 + 2.303 𝑙𝑜𝑔² 𝜎𝑔 𝑙𝑜𝑔 𝑑𝑠𝑛 = 𝑙𝑜𝑔 𝑑′𝑔 − 4.606 𝑙𝑜𝑔² 𝜎𝑔

𝑑𝑣𝑛 𝑙𝑜𝑔 𝑑𝑣𝑛 = 𝑙𝑜𝑔 𝑑𝑔 + 3.454 𝑙𝑜𝑔² 𝜎𝑔 𝑙𝑜𝑔 𝑑𝑣𝑛 = 𝑙𝑜𝑔 𝑑′𝑔 − 3.454 𝑙𝑜𝑔² 𝜎𝑔

𝑑𝑣𝑠 𝑙𝑜𝑔 𝑑𝑣𝑠 = 𝑙𝑜𝑔 𝑑𝑔 + 5.757 𝑙𝑜𝑔² 𝜎𝑔 𝑙𝑜𝑔 𝑑𝑣𝑠 = 𝑙𝑜𝑔 𝑑′𝑔 − 1.151 𝑙𝑜𝑔² 𝜎𝑔

𝑑𝑤𝑚 𝑙𝑜𝑔 𝑑𝑤𝑚 = 𝑙𝑜𝑔 𝑑𝑔 + 8.059 𝑙𝑜𝑔² 𝜎𝑔 𝑙𝑜𝑔 𝑑𝑤𝑚 = 𝑙𝑜𝑔 𝑑′𝑔 + 1.151 𝑙𝑜𝑔² 𝜎𝑔
 Particle number

Particle number, a significant expression is the number of particles per unit weight ‘N’.
3 𝜌
𝜋𝑑𝑣𝑛
Assuming that the particles are spheres, the volume of the single particle is ൗ6 and
3 𝜌
𝜋𝑑𝑣𝑛
mass is ൗ6 g

𝜋𝑑3
𝑣𝑛 𝜌ൗ
6 1𝑔
So, =
1 𝑝𝑎𝑟𝑡𝑖𝑐𝑙𝑒 𝑁

6
N= 3 𝜌
𝜋𝑑𝑣𝑛
 Methods for determining particle size

None of the methods are truly direct methods. Although the microscopic method allows to view the
actual particles but the result obtained is probably no more direct than other methods since only
few particles are ordinarily seen.
 Microscopy

Normal size range detectable

Optical ≥ 0.2-100 µm
Electron ≥ 0.01-100 µm
A sample suspension of particle is spread over a slide and examine under the microscope fitted
with micrometer. The field can be projected onto a screen or detector or photo can be taken
for measurement. The particles are measured along an arbitrarily chosen fixed line, generally
horizontal line across the center of the particle.
A size-frequency curve may be drawn for determination of the statistical diameters of the
distributions.
Disadvantage of the microscopic method is that the diameter obtained is two dimensional.
Depth of the particle measurement is not possible.
 Microscopy

Martin’s diameter: Length of a line that bisects the particle image. The line may be drawn in
any direction but it should be in the same direction for all particles.
Feret’s diameter: The distance between two tangents on opposite side of the particle parallel
to same fixed direction.
Projected diameter: Diameter of a circle with the same area as that of the particle observed
perpendicular to the surface on which the particle rests.
 Sieving

Normal size range detectable ≥ 50 µm

Standard sieves calibrated by the National Bureau of Standards are placed in

descending order i.e., large size sieve is at the top and smallest is at the bottom.
Known weight sample is placed at the top and sieves are shaken either by
agitation, brushing or centrifugation. Weight of the powder retain by each sieve is
determine and percentage retention is calculated. The mean size of the sieve
through which powder passes and retains is calculated. A log normal distribution
curve is plotted using cumulative percent by weight powder retain on a probability
scale against logarithm of mean size. From the table 3 diameter may be obtained.
Sieving
 Sieving

Grade (BP) No. of sieve through which all particles must pass
Coarse Powder 10
Moderately Coarse Powder 22
Moderately Fine Powder 44
Fine Powder 85
Very Fine Powder 120
Ultra Fine Powder 90% of particles ≯5µm & none ≯50µm
 Sedimentation

Stoke’s law:

18𝜂𝑣
𝑑𝑠𝑡 = , where 𝑑𝑠𝑡 is Stoke diameter, v is settling velocity, η is medium
𝑔(𝜌𝑠 −𝜌𝑙 )

viscosity, 𝜌𝑠 is density of solid, 𝜌𝑙 is density of liquid, g is gravitational force (9.81 m

s-2 ).
Liquid medium 200 – 2µm
Air medium 100 – 1µm
 Sedimentation

The Stoke’s equation holds exactly only for spheres falling freely without hindrance and at a
constant rate. The law is applicable for irregular particles relative to the particle size
equivalent to that of sphere falling at the same velocity. The particles must not be
aggregated. The flow of dispersion medium should be laminar or streamline. The falling of
particles should not produce any turbulence and it is indicated by Reynolds number 𝑅𝑒 =
𝑣𝑑𝜌0
, v is the velocity of the fluid, d is the diameter of the pipe, 𝜌0 is the density of the fluid
𝜂0

and 𝜂0 is the viscosity of the fluid. The Stoke’s law can’t be applicable if 𝑅𝑒 > 0.2 since
turbulence appears at this point.
 Sedimentation
Andreasen pipette apparatus

Andreasen apparatus is consists of 550 ml vessel

containing a 10 ml pipette sealed into a ground glass
stopper. When the pipette is in place, its lower tip is
20 cm below the surface of the suspension. 1-2%
suspension of the particle in a medium with suitable
deflocculating agent is introduced into the vessel and
fills up the mark 550 ml. The stoppered vessel is then
shaking to uniform distribution of the particles
throughout the medium and the vessel, stand it at a
constant temperature bath.
 Sedimentation
Andreasen pipette apparatus

At various time intervals, 10 ml samples are withdrawn evaporated and weight of particles is
determined. The particle diameter corresponding to the various time periods is calculated.
The dried sample obtained at a particular time period is the weight fraction having particle
size less than the size obtained at before the time. The weight of each sample is called
weight under size. The sum of the successive weights is called cumulative weight under size.
The data may be represented as frequency distribution plot, Cumulative frequency plot or
log probability plot.
 Sedimentation
SediGraph 5100

SediGraph 5100 instrument has been developed for particle size determination based on
sedimentation. Here low energy X-ray beam is passes through the suspension and the X-ray
pulse is collected by the detector. From the X-ray pulse count the particle size distribution
and the mass of the particles for each particle diameter are derived. The system is
completely automated. It can measure particles of size 0.1-300 µm at 10-40 °C.
 Sedimentation

MATEC Applied Sciences has developed a particle size measurement system for submicron
size 0.015-1.1µm. It consists of a capillary tube through which 1 ml 2-4% suspension
containing suitable surfactant is passes. The suspension must be filtered before feeding
through 5µm filter. The larger particles attain greater velocity than smaller one is the basis
of this instrument. The average particle size of size distribution is determined by number or
volume of the particles. It requires maximum 8 minutes time.
 Elutriation

Separation of lighter particles from

heavier one using vertical air or liquid
stream, particles are collected at
different region of the tube of
elutriator)
Liquid medium 100 – 10µm
Air medium 100 – 2µm
 Elutriation

Fluid flows in the opposite direction of the settling movement of the particles.
Sedimentation is possible for the particles having velocity greater than the liquid. Particles
settling slower will be trapped and moved with liquid overflow. The feed is introduced from
the bottom. Liquid is allowed to move vertically upward direction, particles are settled down
due to the gravitational force. Particles are separated into two fractions in a single column.
Different cross sectional column may be attached and more fractions of particles may be
separated from the overflow fluid containing particles. The fluid flow rate is kept constant
but velocity become decreases due to the increase in cross sectional area. More coarse
particle retain in the first column and fine particles will be retain by the next columns
depending on the liquid velocity and cross sectional area.
 Elutriation

Sedimentation Elutriation
Process of settling particles Separation of lighter particles from
heavier one
Liquid is kept stationary Liquid moving opposite direction to
the sedimentation
Particles moving in the direction of Some particles moving against the
gravitational force direction of gravitational force
Heavier particles settle fast Particles having more settling velocity
settle fast
The time required for separation Liquid velocity and cross sectional
decides size separation area decides size separation
 Coulter counter

Principle: The transient current drop is proportional to

particle volume. Two chambers are filled by electrolyte
solution and chambers are connected by small orifice.
Electrical circuit with detector is connected to the
chambers. Particles are pulled through the orifice
concurrent with electrical current, cause electrolyte
displacement due to particles. That produces a small Detector

change in voltage or current drop, which is proportional to

the particle volume that travels the orifice. Then particle Orifice
Electrolyte solution
diameter is calculated considering the particle as sphere.
Coulter counter

Detector

Orifice
Electrolyte solution
 Newer development

HAIC/Royco light blockage instrument works on the principle of light blockage. The particles
interrupt a light beam and decrease the amount of light that reaches to a photo detector. This
decrease in light transmission produces a voltage pulse proportional to the projected area of each
particle. The results are highly correlated with the National Bureau of Standards reference
particles.
Coulter Model N4 can measure 0.003-0.3µm particles based on the photo correlation
spectroscopy that senses the Brownian motion of the suspended particles. A laser beam is passes
through the sample and sensor detects the light scattered by the particles undergoing Brownian
motion.
Scanning electron microscopy, X-ray analysis and micro computerized mercury porosimetry are
also investigated for particle size determination.
 Porosity

Open intra-particulate voids: Voids within a particle but open to the external environment.

Closed intra-particulate voids: Voids within a particle but closed to the external environment.

Inter-particulate voids: The void space between individual particles.

True volume (𝑽𝒕 ): The total volume of the solid particles excluding all spaces greater than molecular dimension.

Bulk volume (𝑽𝒃 ): The total volume of the solid particles under a particular packing condition during

measurement.

Granular volume or particle volume (𝑽𝒈 ): The total volume of the solid particles including open and closed intra-

particulate voids but excluding inter-particulate voids.

 Porosity

Porosity (E): The ratio of the total volume of void space to the bulk volume of the material.

𝑉𝑣 = 𝑉𝑏 − 𝑉𝑡

𝑉𝑏 −𝑉𝑡 𝑉𝑡
𝐸= =1-
𝑉𝑏 𝑉𝑏

𝑉𝑡
% Porosity = (1 − ) × 100
𝑉𝑏
 Density

The ratio of mass to volume is density

𝑀
True density 𝜌𝑡 =
𝑉𝑡

𝑀
The granular density 𝜌𝑔 =
𝑉𝑔

𝑀
Bulk density 𝜌𝑏 =
𝑉𝑏

𝜌
Relative density 𝜌𝑟 =
𝜌𝑡

𝜌𝑟 is the relative density and it is maximum to 1 when all the air spaces have been eliminated. 𝜌 is
the density of sample powder under specific condition.
 Density

True or absolute density is calculated based on the Boyle’s law 𝑃1 𝑉1 = 𝑃2 𝑉2

The working equation of a gas pycnometer wherein the sample chamber is pressurized first is as
𝑉
follows: 𝑉𝑠 = 𝑉𝑐 + 𝐸𝑃1 , Vs is the sample volume, Vc is the volume of the empty sample
1−
𝑃2
chamber, 𝑉𝐸 is the expanded volume
 Packaging arrangement

Ideal packing arrangements

(i) Closest or rhombohedral

(ii) loosest or cubic packing

 Packaging arrangement

The theoretic porosity of powder consisting of uniform spheres in closest packing is 26% and for

loosest packing is 48%. The real powder particles are neither spherical nor uniform in size. It is to

be expected that the particles of ordinary powders may have an arrangement of either one

identical packaging and the porosity of the powder is in between 30-50%. If particle size is greatly

differ, smaller particle may fill the gaps then the porosity may reduce to below 26%. In powders

containing flocculates or aggregates may form bridge and the porosity may increase to above 48%.

In powder any degree of porosity is possible. Compression of crystalline materials under 100000

lb/in2 pressure can have porosity less than 1%.

 Flow properties

The maximum angle possible between pile of powder and the horizontal plane.

2h
Angle of reposeθ = tan−1 , θ ≤ 30°: free flowing; θ ≥ 40°: poor flow
D

ρT
Hausner’s ratio H = ,H > 1.25: poor flowing
ρB

VB −VT ρT −ρB ρB 1
Carr’sindex C = = =1− = 1− ,
VB ρT ρT H

C > 25: poor flowing and poor tableting,

C < 15: goor flow and good tebleting.

 Bulk density measurement (USP)

Method I—Measurement in a Graduated Cylinder

Procedure— Powder sample is passes through a 1.00-mm (No. 18) screen to break agglomerates.

Sample quantity (M) is 100 g ±0.1% (untapped apparent volume of 150 to 250 mL) using a dry

250-mL graduated cylinder or if it is not possible to use 100 g, the amount of the test sample and

the volume of the cylinder may be modified and the test conditions specified with the results. A

100-mL cylinder is used for apparent volumes between 50 mL and 100 mL. Carefully level the

powder without compacting, if necessary, and read the unsettled apparent volume, Vo, to the

nearest graduated unit. Calculate the bulk density, in g per mL, by the formula: (M) / (Vo).

Generally replicate determinations are desirable for the determination of this property.
 Bulk density measurement (USP)

Method II—Measurement in a Volumeter

ASTM B 329-90 (Scott Volumeter), consists of a top funnel fitted with a 1.00-mm

(No. 18) screen or the screen opening specified in the individual monograph. The

funnel is mounted over a baffle box containing four glass baffle plates over which

the powder slides and bounces as it passes. At the bottom of the baffle box, a

funnel is fixed that collects the powder and allows it to pour into a cup of

specified capacity mounted directly below it. The cup may be cylindrical (25.00 ±

0.05) mL volume with an inside diameter of (30.00 ± 2.00) mm or a square (16.39

± 0.05) mL volume with inside dimensions of (25.4 ± 0.076) mm.

 Bulk density measurement (USP)

Procedure— Allow an excess of powder to flow through the apparatus into the sample receiving

cup until it overflows, using a minimum of 25 cm3 of powder with the square cup and 35 cm3 of

powder with the cylindrical cup. Carefully scrape excess powder from the top of the cup by

smoothly moving the edge of the blade of a spatula perpendicular to and in contact with the top

surface of the cup, taking care to keep the spatula perpendicular to prevent packing or removal

of powder from the cup. Remove any material from the sides of the cup, and determine the

weight, M, of the powder to the nearest 0.1%. Calculate the bulk density, in g per mL, by the

formula: (M ) / (Vo), in which Vo is the volume, in mL, of the cup. Generally replicate

determinations are desirable for the determination of this property.

 Tapped density measurement (USP)

Method I

Procedure— Powder sample is passes through a 1.00-mm (No. 18) screen to break agglomerates. A dry

250-mL glass graduated cylinder (readable to 2 mL) weighing 220 ± 44 g is mounted on a holder weighing

450 ± 10 g. Sample quantity (M) is 100 g ±0.1% using a dry 250-mL graduated cylinder or if it is not

possible to use 100 g, the amount of the test sample and the volume of the cylinder may be modified by

using a suitable 100-mL graduated cylinder (readable to 1 mL) weighing 130 ± 16 g and mounted on a

holder weighing 240 ± 12 g. The modified test conditions are specified with the results. Carefully level

the powder without compacting, if necessary, and read the unsettled apparent volume, Vo, to the

nearest graduated unit.

 Tapped density measurement (USP)

Mechanically tap the cylinder containing the sample by raising the cylinder and allowing it to drop under

its own weight using a suitable mechanical tapped density tester that provides a fixed drop of 14 ± 2 mm

at a nominal rate of 300 drops per minute. Unless otherwise specified, tap the cylinder 500 times initially

and measure the tapped volume, Va, to the nearest graduated unit. Repeat the tapping an additional

750 times and measure the tapped volume, Vb, to the nearest graduated unit. If the difference between

the two volumes is less than 2%, Vb is the final tapped volume, Vf . Repeat in increments of 1250 taps, as

needed, until the difference between succeeding measurements is less than 2%. Calculate the tapped, in

g per mL, by the formula: (M ) / (Vf). Generally replicate determinations are desirable for the

determination of this property.

 Tapped density measurement (USP)

Method II

Proceed as directed under Method I except that a suitable mechanical tapped density tester that

provides a fixed drop of 3 mm (±10%) at a nominal rate of 250 drops per minute is used.
Thank you