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Particle-Size Distribution, Part I

Representations of Particle
Shape, Size, and Distribution
Harry G. Brittain

Particle-size determinations are undertaken
to obtain information about the size
characteristics of an ensemble of particles.
Because the particles being studied are not
usually the exact same size, information is
required regarding the average particle size
and the distribution of sizes about this
average. However, the concept of particle
size is irrevocably derived from aspects of
particle shape and morphology because the
idea of a particle diameter proceeds from
preconceived shape factors.
I
n the July 2001 Pharmaceutical Technology article about
particle-size determination, the question of what constitutes
a correct method for the determination of particle-size dis-
tributions was addressed (1). A correct method was defined as
one whose sample was obtained by an appropriate sampling pro-
cedure, in which the sample was prepared properly and intro-
duced into the instrument, and in which all instrumental para-
meters were used correctly for the analysis. It also was pointed
out that all of the correct (but differing) particle-size results ob-
tained through various methodologies are equally accurate, but
each method simply might be expressing its correct results in
different terms. When viewed in this light, the decision about
which particle-size methodology is most appropriate for a given
situation can be seen as a simple matter of accuracy versus pre-
cision. If absolute accuracy is most important, then one must
conduct rigorous research to verify that the method finally
adopted does indeed yield particle-size results that are absolutely
indicative of the characteristics of the bulk material. If, however,
one is more interested in developing profiles of lot-to-lot vari-
ability, then the use of any of the available methods that yields
correct results is appropriate.
The next several articles in the Pharmaceutical Physics col-
umn series will examine a variety of correct methodologies that
can be used to deduce information about the shape and size
distribution of particles. However, one cannot begin to address
those topics without a prior exposition of what is meant by the
shape and size of the particles that consitute a powdered solid.

Harry G. Brittain, PhD, is the director of
the Center for Pharmaceutical Physics, 10
Charles Road, Milford, NJ 08848, tel. 908.
996.3509, fax 908.996.3560, hbrittain@
earthlink.net. He is a member of Pharma-
ceutical Technologys Editorial Advisory
Board.
38 Pharmaceutical Technology DECEMBER 2001
Particle shape
It is not possible to discuss rationally the size of a particle or
any distribution associated with the sizes of an ensemble of par-
ticles without first considering the three-dimensional charac-
teristics of the particle itself. This is because the size of a parti-
cle is expressed either in terms of linear dimension characteristics
derived from its shape or in terms of its projected surface or
volume. As will be shown, some methods of expressing parti-
cle size discard any concept of particle shape and instead ex-
press the size in terms of some type of equivalent spherical size.
An appropriate starting place for a discussion of particle shape
can be found in USP General Test ^776& (see Figure 1) (2). In the
shape performance aspect of this particular test procedure, USP
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requires that for irregularly shaped particles, characterization plate: flat particle of similar length and width but with greater
of particle size must also include information on particle shape. thickness than flakes
The general method defines several descriptors of particle shape lath: long, thin, blade-like particle

(see Figure 2). The USP definitions of these shape parameters are equant: particles of similar length, width, and thickness; both

acicular: slender, needle-like particle of similar width and
thickness
columnar: long, thin particle with a width and thickness that
are greater than those of an acicular particle
flake: thin, flat particle of similar length and width
cubical and spherical particles are included.
In ordinary practice, one rarely observes discrete particles but
typically is confronted with particles that have aggregated or ag-
glomerated into more-complex structures. USP provides sev-
eral terms that describe any degree of association:
lamellar: stacked plates

aggregate: mass of adhered particles

agglomerate: fused or cemented particles

conglomerate: mixture of two or more types of particles

spherulite: radial cluster

Plate Tabular
drusy: particle covered with tiny particles (2).

The particle condition also can be described by another se-

ries of terms:
edges: angular, rounded, smooth, sharp, fractured

optical: color, transparent, translucent, opaque

defects: occlusions, inclusions.

Furthermore, surface characteristics can be described as

cracked: partial split, break, or fissure

smooth: free of irregularities, roughness, or projections

Equant Columnar porous: having openings or passageways

rough: bumpy, uneven, not smooth

pitted: small indentations.

The pharmaceutical descriptors of particle shape are derived

Blade from the general concept of crystallographic habit. The exact
shape acquired by a crystal will depend on various factors such
as the temperature, pressure, and composition of the crystal-
Acicular lizing solution. Nevertheless, precipitation of a given compound
generally creates a characteristic shape or outline. Because the
Figure 1: Description of particle shape as defined by USP. faces of a crystal must reflect the internal structure of the solid,

Lamellar Tabular Equant Columnar Acicular

Isometric
Tetragonal

0001
Hexagonal

1011 0111

Figure 2: Growth along certain crystal directions can profoundly alter the characteristic habit of various crystals.
40 Pharmaceutical Technology DECEMBER 2001 www.phar mtech.com
 (a) (b) (c)
Feret's diameter
th
ng
Le
Projected
Martin's area
diameter diameter
W
idt
h
Figure 3: Some commonly used descriptors of particle size.
the angles between any two faces of a crystal will remain the
same even if the crystal growth is accelerated or retarded in one
direction or another (see Figure 2). Optical crystallographers
usually will catalogue the various crystal faces and document
the angles between them as they identify the crystal system to
which the given particle belongs. When the particle is particu-
larly well formed, a description of symmetry elements also is
compiled.
For many individuals, however, the concept of qualitative
shape descriptors has proven inadequate, and this deficiency
has necessitated the definition of more quantitatively defined
shape coefficients (3). For instance, Heywood describes the elon-
gation ratio, n, as
[1]
and the flakiness ratio, m, as
[2]
in which T is the particle thickness (the minimum distance be-
tween two parallel planes that are tangential to opposite surfaces
of the particle), B is the breadth of the particle (the minimum
distance between two parallel planes that are perpendicular to
the planes defining the thickness), and L is the particle length
(the distance between two parallel planes that are perpendicu-
lar to the planes defining thickness and breadth) (4).
Particle size
It really is not possible to continue a discussion of particle shape
or size without first developing definitions of particle diame-
ter. This step is, of course, rather trivial for a spherical particle
because its size is uniquely determined by its diameter. For ir-
regular particles, however, the concept of size requires defini-
tion by one or more parameters. It often is most convenient to
discuss particle size in terms of derived diameters such as a
spherical diameter that is in some way equivalent to some size
property of the particle. These latter properties are calculated
by measuring a size-dependent property of the particle and re-
lating it to a linear dimension.
Certainly the most commonly used measurements of parti-
cle sizes are the length (the longest dimension from edge to edge
of a particle oriented parallel to the ocular scale) and the width
(the longest dimension of the particle measured at right angles
to the length). Intuitive as these properties may be, their defin-
ition still is best shown in Figure 3a. Closely related to these prop-
erties are two other descriptors of particle size: Ferets diameter,
42 Pharmaceutical Technology DECEMBER 2001
which is the distance between imaginary parallel lines tan-
gent to a randomly oriented particle and perpendicular to
the ocular scale, and Martins diameter, which is the diam-
eter of the particle at the point that divides a randomly ori-
ented particle into two equal projected areas (see Figure
3b).
The coordinate system associated with the measurement
is implicit in the definitions of length, width, Ferets di-
ameter, and Martins diameter because the magnitude of
these quantities requires some reference point. As such,
these descriptors are most useful when discussing particle size
as measured by microscopy because the particles are immobile.
Defining spatial descriptors for freely tumbling particles is con-
siderably more difficult and hence requires the definition of a
series of derived particle descriptors. However, given the popu-
larity of techniques such as electrozone sensing or laser light
scattering, derived statements of particle diameter are extremely
useful.
All of the derived descriptors for particle size begin with the
homogenization of the length and width descriptors into either
a circular or spherical equivalent and make use of the ordinary
geometrical equations associated with the derived equivalent.
For instance, the perimeter diameter is defined as the diameter
of a circle having the same perimeter as the projected outline of
the particle. The surface diameter is the diameter of a sphere hav-
ing the same surface area as the particle, and the volume dia-
meter is defined as the diameter of a sphere having the same vol-
ume as the particle. One of the most widely used derived
descriptors is the projected area diameter, which is the diameter
of a circle having the same area as the projected area of the par-
ticle resting in a stable position. The concept of projected area
diameter is illustrated in Figure 3c.
Several other derived descriptors of particle diameter have
been used for various applications. For instance, the sieve dia-
meter is the width of the minimum square aperture through
which the particle will pass. Other descriptors that have been
used are the drag diameter, which is the diameter of a sphere hav-
ing the same resistance to motion as the particle in a fluid of the
same viscosity and at the same velocity; the free-falling diameter,
which is the diameter of a sphere having the same density and
the same free-falling speed as the particle in a fluid of the same
density and viscosity; and the Stokes diameter, which is the free-
falling diameter of a particle in the laminar-flow region.
Distribution of particle sizes
All analysts know that the particles that constitute real sam-
ples of powdered substances do not consist of any single type
but instead will generally exhibit a range of shapes and sizes.
Particle-size determinations therefore are undertaken to ob-
tain information about the size characteristics of an ensemble
of particles. Furthermore, because the particles being studied
are not the exact same size, information is required about the
average particle size and the distribution of sizes about that
average.
One could imagine the situation in which a bell-shaped curve
is found to describe the distribution of particle sizes in a hy-
pothetical sample; this type of system is known as the normal
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 (a) (b) in each size fraction is identified, and
20

Cumulative distribution
100 then one calculates the percentage of par-
Number frequency

15 80 ticles in each size fraction. This calcula-

60 tion yields the particle size histogram
10 (see Figure 4a). The number frequency
40
5 ordinarily is used to construct a cumu-
20
lative distribution, which can be as-
0 0 cending or descending depending on the
0 10 20 30 40 50 60
nature of the study and what informa-
Particle size (mm) Particle size (mm)
tion is required (see Figure 4b).
The arithmetic mean of the ensemble
of particle diameters is calculated using
Figure 4: Particle-size representations for a hypothetical normal distribution. Shown are (a) the
the relation
frequency distribution and (b) the cumulative distribution.
[3]

in which n is the number of particles

(a) (b)
20 20 having a diameter equal to di. The stan-
Number frequency

Number frequency

dard deviation in the distribution then

15 15
is calculated using
10 10
[4]
5 5

0 0
0 10 20 30 40 50 60 70 In the example shown in Table I, one cal-
10 100
Particle size (mm) culates that dav 5 30.2 mm and that s =
Particle size (mm)
1.1.
The most commonly occurring value
Figure 5: Particle-size representations for a hypothetical log-normal distribution, plotted on a (a) in the distribution is the mode, which is
linear scale and on a (b) logarithmic scale. the value at which the frequency repre-
sentation is a maximum value. The me-
dian divides the frequency curve into two equal parts and equals
Table I: Particle composition of a hypothetical sample the particle size at which the cumulative representation equals
exhibiting a normal distribution. 50%. In a rigorous normal distribution, the mean, mode, and
Size Number Number Percent Percent median have the same value. For a slightly skewed distribution,
(mm) in Band Frequency Less Than Greater Than however, the following approximate relationship holds:
5 50 1.67 1.67 98.33
10 90 3.00 4.67 95.33 [5]
15 110 3.67 8.33 91.67
20 280 9.33 17.67 82.33 It would be highly advantageous if powder distributions could
25 580 19.33 37.00 63.00 be described by the normal distribution function because all of
30 600 20.00 57.00 43.00 the statistical procedures developed for Gaussian distributions
35 540 18.00 75.00 25.00 could be used to describe the properties of the sample. How-
40 360 12.00 87.00 13.00 ever, unless the range of particle sizes is extremely narrow, most
45 170 5.67 92.67 7.33 powder samples cannot be described adequately by the normal
50 120 4.00 96.67 3.33 distribution function. The size distribution of the majority of
55 60 2.00 98.67 1.33 real powder samples usually is skewed toward the larger end of
60 40 1.33 100.00 0.00 the particle-size scale. Such powders are better described by the
Total 3000 100 log-normal distribution type. This terminology arose because
when the particle distribution is plotted by means of the loga-
distribution. Samples that conform to the characteristics of a rithm of the particle size, the skewed curve is transformed into
normal distribution are described fully by a mean particle size one closely resembling a normal distribution (see Figure 5).
and the standard deviation. Table I shows an example of a sam- The distribution in a log-normal representation can be com-
ple exhibiting a normal distribution in which 3000 particles pletely specified by two parameters: the geometric median par-
have been sorted according to an undefined determiner of their ticle size (dg) and the standard deviation in the geometric mean
size. In the usual data representation, the number of particles
Pharmaceutical Technology DECEMBER 2001 43
 in which n is the number of particles hav-
(a) 30 (b) ing particle size equal to di. Two samples
% mass
100 having identical dg and sg values can be
frequency 80 said to have been drawn from the same
% in bond

20

% finer
% number
frequency 60 Cumulative total population and exhibit properties
% mass of characteristics of the total population.
10 40
Cumulative
20 % number In many applications, particle-size re-
0 0 sults are processed by plotting the cu-
0 15 30 45 60 75 mulative frequency data on a logarith-
Size (mm) Size (mm) mic scale. If a straight line is obtained,
the particle-size distribution is said to
obey the log-normal function. The value
Figure 6: Particle-size representations for a hypothetical log-normal distribution. Shown are (a) of dg is equal to the 50% value of the cu-
the frequency distribution and (b) the cumulative distribution. Each contains the difference mulative distribution. The value of sg
obtained when processing the data in terms of either particle number or particle mass. is obtained by dividing the 84.1% value
of the distribution by the 50% value.
Although the distribution in the log-
normal representation is specified completely by the geomet-
(a) US M
ric median particle size and the geometric mean standard de-
standard s M Ms viation, a number of other average values have been derived to
10 2,000
Mesh (US standard sieve series)

12 1,500 define useful properties. These values are especially useful when
16
1,000 the physical significance of the geometric median particle size
20
is not clear. The arithmetic mean (dav) particle size is defined
30
40
500 as the sum of all particle diameters divided by the total num-
400
50 300 ber of particles and is calculated using Equation 3. The surface
70 200 mean (ds) particle size is defined as the diameter of a hypo-
100 150
thetical particle having an average surface area and is calculated
140 100
200
using
270 50
325
0.5 1 2 5 10 20 30 40 50 60 70 80 90 95 98 99 99.5 [7]
Cumulative percentage of undersize particles

(b) US M
standard s M Ms The volume mean (dv) particle size is the diameter of a hypo-
10 2,000
thetical particle having an average volume and is obtained from
Mesh (US standard sieve series)

12 1,500
16
1,000
20
[8]
30
500
40 400
50 300
70 200
The volume-surface mean (dvs) particle size is the average size
100 150 based on the specific surface per unit volume and is calculated
140 100 using
200
270 50
325
0.5 1 2 5 10 20 30 40 50 60 70 80 90 95 98 99 99.5 [9]
Cumulative percentage of undersize particles

Figure 7: Particle-size representations plotted in a log-probability
format for (a) a single hypothetical log-normal distribution and for
(b) a hypothetical sample containing two log-normal distributions
whose average particle size differs by ;50%.
(sg). The geometric median is the particle size pertaining to the
50% value in the cumulative distribution and is calculated using
44 Pharmaceutical Technology
For the distribution plotted in Figure 5, one can calculate that
dg 5 32.91 mm, dav 5 34.42 mm, ds 5 35.93 mm, dv 5 37.43 mm,
and dvs 5 40.62 mm.
Various types of physical significance have been attached to
the various expressions of particle size. For chemical reactions,
the surface mean is important, although for pigments the vol-
ume mean value is the appropriate parameter. Deposition of
particles in the respiratory tract is related to the weight mean
diameter, and the dissolution of particulate matter is related to
[6] the volume-surface mean.
Particle-size distributions can be sorted according to the mass
(or volume) of the particles contained within a given size band
DECEMBER 2001 www.phar mtech.com
 Recommended reading
or to the number of particles contained in the same size R.R.Irani and C.F.Callis, Particle Size: Measurement, Interpretation, and Application (John
band. With substances having real density values, the dis- Wiley & Sons,New York,1963).
tribution of the same ensemble of particles can look quite Z.K.Jelinek,Particle Size Analysis (Ellis Horwood Ltd.,Chichester,1970).

different depending on how the data are plotted. Figure J.D.Stockham and E.G.Fochtman, Particle Size Analysis (Ann Arbor Science Publishers,
6 shows the frequency and cumulative distribution plots Ann Arbor,MI,1977).
for the same sample, but the data have been separately B.H.Kaye,Direct Characterization of Fine Particles (John Wiley & Sons,New York,1981).
processed in terms of the mass and particle numbers. H.G.Barth,Modern Methods of Particle Size Analysis (John Wiley & Sons,New York,1984).

Unfortunately not every powdered sample is charac- T.Allen,Particle Size Measurement, 5th ed.(Chapman and Hall,London,1997).

terized by the existence of a single distribution, and the

character of real samples can be quite complicated. Recogniz- recommended references to additional information (see Rec-
ing the existence of multimodal distributions is not always a ommended reading sidebar). Most highly recommended are
straightforward process, but their existence often can be detected the various editions of Particle Size Measurement by Allen be-
by plotting the data on log-probability paper. The existence of cause they contain some of the most detailed and informative
more than one particle population is indicated by a change in expositions available about these topics. However, the scope of
the slope of the line. Figure 7 shows a single log-normal distri- the discussion in this opening article provides a sufficient basis
bution and a multimodal sample consisting of two populations for the expositions of the various methodologies that will fol-
whose mean differed by approximately 50%. The break in the low in subsequent installments of this column.
log plot is clearly evident, but if one were to simply plot the lat-
ter sample in either a frequency or cumulative view, one would References
not have been able to detect the existence of two particle-size 1. H.G. Brittain, What is the Correct Method to Use for Particle-Size
populations in the sample. Determination? Pharm. Technol. 25 (7), 9698 (2001).
2. Optical Microscopy, General Test ^776&, USP 24 (The United States
Pharmacopoeial Convention, Rockville, MD, 2000), pp. 19651967.
Summary 3. T. Allen, Particle Size Measurement (Chapman and Hall, London, 3rd
This rather simplified discussion of particle shape, size, and dis- ed.,1981) pp. 107120.
tribution represents only an introduction to the topic. Inter- 4. H. Heywood, J. Pharm. Pharmacol. (S15) 56T, (1963). PT
ested readers should consult the primary sources in the list of

Circle/eINFO 25
Pharmaceutical Technology DECEMBER 2001 45