Powder Technology 132 (2003) 57 – 63

www.elsevier.com/locate/powtec

Use of X-ray tomography to study the porosity

and morphology of granules
Leon Farber a,*, Gabriel Tardos b, James N. Michaels a
a
Merck and Co., Inc., P.O. Box 4, WP78A-31, West Point, PA 19486, USA
b
Department of Chemical Engineering, The City College of the City University of New York, New York, NY 10031, USA
Received 7 May 2002; received in revised form 21 August 2002; accepted 28 January 2003

Abstract

X-ray computed tomography (XRCT) is a technique that uses X-ray images to reconstruct the internal microstructure of objects. Known
as a CAT scan in medicine, it has found wide application for whole-body and partial-body imaging of hard tissues (e.g., bone). A modern
tabletop XRCT system with a resolution of about 4 Am was used to characterize some pharmaceutical granules. Total porosity, pore size
distribution, and geometric structure of pores in granules produced using different conditions and materials were studied. The results were
compared to data obtained from mercury porosimetry. It was found that while XRCT is less precise in the determination of total porosity in
comparison to mercury porosimetry, it provides detailed morphological information such as pore shape, spatial distribution, and connectivity.
The method is nondestructive and accurate down to the resolution of the instrument.
Tomographic images show that the pore network of individual granules comprises relatively large cavities connected by narrow pore
necks. The major structural difference between granules produced at different conditions of compaction and shear is a reduction in the pore
neck diameter; the cavity size is relatively insensitive to these conditions. Comparison of pore size distributions determined from
tomographic images and mercury porosimetry indicates that mercury intrusion measures the pore neck size distribution, while tomography
measures the true size distribution of pores ca. 4 Am or larger (the instrument resolution).
D 2003 Elsevier Science B.V. All rights reserved.

Keywords: X-ray tomography; Imaging; Granules; Internal microstructure

1. Introduction pores. The presence of pores controls such basic properties

X-ray computed tomography (XRCT) is a nondestructive
technique that measures variations in material density. The
technique uses a set of two-dimensional shadow X-ray
images of an object to reconstruct its three-dimensional
structure using a mathematical algorithm [1 –4]. The recent
development of powerful, yet miniaturized, dedicated X-ray
sources has resulted in production of compact tabletop X-ray
systems with a resolution of several microns. This advances
the technique into the ‘‘microscopy’’ category and makes it
feasible to apply this technique for characterization of a wide
range of materials in laboratory settings. We report in this
paper on the application of a microtomography system for
studying the microstructure of pharmaceutical granules
(agglomerates made of individual particles).
An important characteristic of granules is their porosity
or void fraction as well as the size and spatial distribution of
* Corresponding author. Tel.: +1-215-6520258; fax: +1-215-6522132.
as wet and dry strength, dissolution, and disintegration in a
liquid medium. Common methods to characterize the pore
structure of materials include mercury porosimetry and gas
adsorption techniques. In mercury porosimetry, accessible
pore volume is determined directly from the intrusion
volume of mercury into the material at high pressure, and
the pore size distribution can be determined from the
intrusion volume –pressure curve by assumption of a model
for pore geometry (typically parallel cylindrical pores). In
gas adsorption methods, total pore volume is determined
from the area of the hysteresis loop in adsorption/desorption
isotherms, and the pore size distribution can be computed
from the isotherm by assumption of appropriate pore vol-
ume and gas adsorption models.
X-ray tomography is a technique that can be used as an
alternative way to determine both porosity and pore size
distribution within an object. The microstructure of an entire
granule or a tablet can be visualized down to details
comparable to the resolution of the instrument in a non-

0032-5910/03/$ - see front matter D 2003 Elsevier Science B.V. All rights reserved.
doi:10.1016/S0032-5910(03)00043-3
58 L. Farber et al. / Powder Technology 132 (2003) 57–63
destructive way. As a result, individual pores are visualized
and the true internal morphology of granules is revealed.
Thus, in principle, the pore size distribution can be deter-
mined without the assumption of a particular model of pore
geometry.
The goal of the present work was to compare X-ray
tomography and mercury porosimetry for characterizing
porosity and pore size distributions in granules.
2. Experimental
2.1. Materials
Granules for the study were fabricated mannitol- and
lactose-microcrystalline cellulose (Avicel, FMC Corp.)-
based blends using various amounts of water and different
binders. Fabrication techniques included drop granulation in
a very-low-shear granulator (VLSG) and high-shear granu-
lation in a 2-l Fukae granulator. Details on composition and
fabrication conditions for each sample are shown in Table 1.
2.2. Mercury porosimetry
Accessible porosity and pore size distribution were
measured for all samples using the Quantacrome Pore-
Master 60. Experiments were performed using a standard
procedure: samples were placed in a calibrated glass cell,
degassed using a rotary vacuum pump, and then mercury
was forced into the cell. The intrusion pressure was
increased and the corresponding volume of mercury
injected into the cells was recorded. The cell was weighed
before and after filling. The porosity was calculated using
the total volume of mercury intruded into the sample and
the true density of the material (q = 1.514, 1.552, and
1.550 g/cm3 for mannitol, lactose, and Avicel, respectively
[5]). Although part of the mannitol and lactose dissolves
during processing and then precipitates out on drying,
most likely as amorphous materials, it was estimated that
the error that could be associated with the density differ-
Table 1
Materials and processing conditions
Sample Material Processing
HS1 Mannitol SD-200 High-shear granulator; water as binder,
pumped through 1/8-in. tube at 12 ml/min
added over 4 min, 600/1800 blade/chopper
rpm, wet-massed for 1 min, 16% moisture
in wet granule measured in situ
HS2 Mannitol SD-100 High-shear granulator; 3% HPC in solution,
drop granulation at 200/600 blade/chopper
rpm, 21.9/23.2% moisture of wet granule
measured in situ
LS Lactose/Avicel, Drop granulation in a very-low-shear
60%/40% granulator (VLSG); 3% HPC solution in
water as binder
Table 2
Porosity and pore size in different samples
Sample Porosity (%) Pore size (Am)
P XRCT Pa XRCT
HS1 14.6 12.4 0.1 – 0.2 62a
HS2 58.7 58.3 33 31/118b
LS 61.0 58.1 45 62/310b
P = mercury porosimetry; XRCT = X-ray computed tomography.
a
Mode of the volume based pore size distribution.
b
Projected channel width/cavity diameter as unfolded from recon-
structed cross-sections.
ence between the amorphous and the crystalline form of
each material is less than 2%. Pore size distribution was
obtained assuming parallel, cylindrical nonintersecting
pores of different radii using PoreMaster’s standard soft-
ware package.
2.3. X-ray tomography and image analysis
X-ray tomography was performed using the Skyscan
1072 high-resolution X-ray microtomograph (Skyscan, Bel-
gium) that has a resolution better than 4 Am. Samples were
scanned in the 0 –180j interval using a 0.9j scan step at 4-
W power settings. Typical acquisition time was about 1 h.
Median filtration and geometrical correction were applied
during acquisition. Cross-sectional pixel size was 11 and
3.42 Am for samples LS and HS, respectively. Cross-sec-
tional and 3-D images were reconstructed using the Skyscan
software package. Overall and cross-sectional porosities
were calculated using the reconstructed images and the
Skyscan software package. Because of the high porosity
of the samples, the original reconstructed images had
relatively low signal-to-noise ratio, which resulted in an
uncertainty of up to 10% in porosity calculation.
The volumetric pore size distribution of sample HS1 was
unfolded from an equivalent projected area diameter distri-
bution assuming spherical pore shape and following an
algorithm described in Ref. [6]. This equivalent projected
area diameter distribution was obtained directly from cross-
sectional XRCT images via Image-Pro software. The poros-
ity in samples HS2 and LS appears in the reconstructed
cross-sectional images as continuous networks of intercon-
nected channels and cavities, so that the above projected
area approach for pore size determination could not be used.
A special linear intercept method was employed (see
Appendix A and Refs. [7,8]) to evaluate channel width
and cavity size in these cases. Intercept frequency distribu-
tion was obtained from cross-sectional XRCT pictures using
Image-Pro software. The distance between ‘‘probing’’ lines
for samples HS2 and LS corresponded to 180 and 350 Am,
respectively. Overall count was obtained by combining the
data from several cross-sections with the total count of more
than 4000. The resultant size distribution plots were
unfolded from the frequency distribution plots assuming
spherical geometry of voids.
 L. Farber et al. / Powder Technology 132 (2003) 57–63 59

3. Results and discussion
The total porosity and pore size distribution for different
granules computed from the tomographic images and mer-
cury porosimetry data are compared in Table 2. The two
techniques yield very similar overall porosities; however,
the measured pore sizes differ by as much as two orders of
magnitude.
The source of the discrepancy in the values of the
average pore size can be understood from the analysis of
tomographic cross-sections of, for example, granule HS1
(see Fig. 1). The shadow X-ray image of the granule is
presented in Fig. 1a while typical reconstructed cross-sec-
tional images are shown in Fig. 1b and c at different
magnifications. Black areas represent dense material while
white areas are pores. Most of the pores in the images

Fig. 1. Tomographic images and pore size distributions of granules produced under high shear in the Fukae mixer: (a) X-ray shadow image; (b) typical
reconstructed cross-sectional image; (c) high-magnification image of area in the box in (b); (d) pore size distribution calculated from tomographic image; and
(e) pore size distribution as measured by mercury porosimetry.
60 L. Farber et al. / Powder Technology 132 (2003) 57–63

appear occluded, as clearly evident in Fig. 1c. The overall
porosity determined from the cross-sectional images and a
reconstructed 3-D image is about 12.4%. The volume-based
pore size distribution from XRCT, calculated from the
equivalent projected area in Fig. 1b, is shown in Fig. 1d
where the mode is close to dv = 62 Am.
A total accessible porosity of about 15% was determined
from the amount of mercury intruded into the sample at high
pressure (33,000 psi). The pore size distribution from
mercury porosimetry shown in Fig. 1e has a mode of
0.1 –0.2 Am and indicates that most pores are smaller than
1 Am in diameter. This size is clearly below the resolution of
the X-ray tomograph and, hence, practically no pores should
be visible in the X-ray tomographic images. Yet, as the
cross-sectional XRCT images in Fig. 1b and c clearly show,
pores of much larger size are present. To ascertain that both
instruments ‘‘see’’ the same porosity, an additional experi-
ment (‘‘mercury pycnometry’’) was performed by forcing
mercury into the sample at a low pressure of only 50 psi.
This pressure is not sufficient for mercury to penetrate
inside the granules; thus, mercury simply fills the interstitial
volume between particles in the porosimetry cell. The

Fig. 2. Tomographic images and pore size distribution of a granule produced under low shear conditions in the Fukae mixer: (a) typical reconstructed cross-
sectional image; (b) high-magnification image of area in the box in (a); (c) linear intercept distribution; (d) unfolded pore size distribution; and (e) pore size
distribution as measured by mercury porosimetry.
 L. Farber et al. / Powder Technology 132 (2003) 57–63 61

volume of granules is determined from the difference of the
empty cell volume and the low-pressure intrusion volume;
the porosity is then calculated from this measurement and
the weight and true density of the granules (mannitol in this
case). The porosity thus determined was 15.9% or only
slightly higher than the porosity obtained from high-pres-
sure intrusion and from X-ray imaging. Since all three
measurements yield essentially the same total porosity, we
conclude that porosimetry and tomography interrogate the
same pore space.
It appears, therefore, that the pores imaged with XRCT
account for the major share of the overall pore volume in the
granule. Since mercury is able to fill these pores only at
sufficiently high pressure, they must be connected to each
other and to the surface of the granule. However, the pores
must be connected by only small channels since mercury
intrusion is ‘‘delayed’’ until the external pressure reaches the
pressure, allowing intrusion into orifices smaller than ca. 1
Am. At this point, the whole sample is filled rather quickly,
producing a peak at 0.1– 0.2 Am in the pore size distribu-
tion. The porosity values measured by the XRCT and
mercury porosimetry (12.5% and 14.6%, respectively) are
practically equal given the uncertainty in XRCT measure-
ments.
Fig. 2 shows a typical XRCT cross-sectional image of a
granule produced under conditions of much lower shear
(blade/chopper speeds of 200/600 rpm were used instead of
600/1800 rpm used to produce the granule in Fig. 1). The
overall porosity of the granule is much larger, about 58% as
determined from both mercury porosimetry and XRCT. The
pore morphology is different, with large internal pores
separated by clearly visible channels. Fig. 2b shows a
portion of a typical cross-section at higher magnification.
Relatively large ‘‘chambers’’ (pores) of 80 – 120 Am in

Fig. 3. Granule made in the very low shear granulator: (a) typical side view X-ray image; (b) vertical cross-sectional slice of 80 Am thick (3-D reconstruction;
mannitol is in gray); (c – e) reconstructed 2-D horizontal slices X1 – X3 (mannitol is in dark gray, slice thickness is 11 Am); and (f) enlargement from cross-
section (e).
62 L. Farber et al. / Powder Technology 132 (2003) 57–63
diameter (identified by capital letters from A to D) are seen
to be connected to each other via orifices that appear about
20 –40 Am in diameter.
The linear intercept distribution analysis for this sample
is shown in Fig. 2c and d. Fig. 2c shows an uncorrected
distribution of ‘‘probing’’ lines with the void space on the
cross-sectional images. Fig. 2d gives the volumetric distri-
bution of void space obtained by a deconvolution of the
previous distribution [6]. This correction is required since
even mono-sized equal spheres yield a distribution if they
are evaluated by a linear one-dimensional probe. One has to
also note that the result in Fig. 2d is a diameter-equivalent
pore size distribution calculated from the linear distribution
and, as seen, there are two peaks in the pore size that
correspond to channels and cavities, respectively. Typical
channel width is in the range of 20 –40 Am, whereas cavities
are close to 120 Am in size as can be seen directly with the
naked eye in Fig. 2b. The mode of the pore size distribution
measured by mercury porosimetry is 33.5 Am (see Fig. 2e).
A comparison of the XRCT pictures in Figs. 1 and 2
demonstrates clearly that the size of the pores does not
change dramatically as both the material and processing
conditions are changed, even though this could easily (but
erroneously) be inferred from the mercury intrusion pore
size distributions. The major difference in granules pro-
duced under different conditions is not the size of the pores,
but the way they are connected.
A further example deals with granules produced in the
very-low-shear granulator from a 60%/40% lactose/Avicel
mixture using a 3% HPC solution in water. Fig. 3 shows a
side view (Fig. 3a), a vertical slice (Fig. 3b), and three
representative horizontal cross-sections of a typical LS
granule (Fig. 3c– e). Each cross-section represents an 11-
Am-thick slice of the material. The pore structure in the
granule is clearly revealed. The porosity appears as contin-
uous networks of interconnected channels and cavities. Fig.
3f shows a portion of a reconstructed cross-section at higher
magnification. Relatively large ‘‘chambers’’ (pores) of 100–
200 Am in diameter (identified by capital letters from A to
E) are connected to each other via orifices that are about
30 –70 Am in diameter. The pores are not uniformly dis-
tributed through the granule: a large void space exists in the
central part of the granule. The total porosity of 58%
computed from the full set of tomographic images of the
granule agrees well with the total porosity of 61% measured
by mercury porosimetry (Table 2). However, porosimetry, as
performed in the PoreMaster 60, did not give any indication
of the large void space in the middle of the granule nor
about the channels/cavity morphology. The pore size dis-
tribution obtained from the porosimeter contains only one
peak at about 45 Am. This clearly demonstrates that mercury
porosimetry yields ‘‘neck’’ sizes and not effective pore size
distributions.
Another feature of the tomograph is demonstrated in Fig.
4, which shows a composite picture of a horizontal slice 100
Am thick from the bottom part of the above granule. The
Fig. 4. A 3-D image of a 100-Am-thick slice reconstructed from 10 adjacent
horizontal cross-sectional images of granule shown in Fig. 3.
slice was reconstructed by combining 10 images of the kind
shown in Fig. 3c. Light gray areas represent the solids.
Some pores are depicted in black while others are depicted
in dark gray so that they can be analyzed separately. Using
this procedure, different constituents of a sample (e.g., pores
and solid phases of different densities) as well as the same
constituent but in different locations can be reconstructed
and analyzed separately.
It is clear from the above that in order to characterize the
porosity of granules fully and accurately, both XRCT and
porosimetry should be used in a complementary way.
Porosimetry can provide an accurate measurement of overall
connected porosity down to nanometer scale and the ‘‘pore
neck distribution’’. XRCT, on the other hand, can provide
qualitative morphological information about pore shape,
spatial distribution, and connectivity of pores. Tomography
also provides a quantitative measure of the actual pore size
distribution and total porosity; however, instrument resolu-
tion limits these measurements to pores greater than ca. 4
Am in diameter.
4. Conclusions
X-ray tomography is a very promising tool for character-
ization of porosity and morphology of granules, compacts,
and tablets. Although XRCT is inferior in precision to
porosimetry for measuring total porosity, it provides mor-
phological information such as pore shape, spatial distri-
bution, and connectivity that cannot be measured by
mercury intrusion. In addition, it provides an accurate
measurement of true pore size distribution. This is in
contrast to mercury porosimetry, which measures the diam-
eter of pore ‘‘necks’’ only. The method is nondestructive
and quite accurate down to the resolution of the instrument
of about 4 Am.
 L. Farber et al. / Powder Technology 132 (2003) 57–63 63

Acknowledgements

Many researchers have contributed to the above work by

suggesting materials and granulation conditions or just
helpful advice. The authors wish to especially thank (in no
particular order) Patricia Hurter, Dafni Bika, Michael
Gentzler, and Karen Hapgood for their advice and help.

Appendix A . Application of the ‘‘linear intercepts

method’’ for analysis of interconnected porosity

Standard software for porosity analysis is usually ‘‘area-

based’’ and can only analyze isolated pores since intercon-
nected porosity is treated as a single pore and thus cannot be
analyzed in terms of porosity distribution. The major
advantage of the linear intercepts method is that it allows
to analyze interconnected porosity. A detailed description of
the method is given in Ref. [7]. This appendix provides a
brief description of the method and its particular application
to this work. In essence, a set of probing lines is super-
imposed on a cross-sectional image of an object. If it can be
assumed that the sample is isotropic, uniform, and random,
a grid of parallel straight lines can be used for the analysis.
An example is shown in Fig. 5 where a grid of three lines
(L1 – L3) is superimposed over a cross-sectional image
taken from Fig. 2b. The lengths of intercepts obtained by
‘‘probing’’ lines intersecting ‘‘void space’’ (such as Lij in
Fig. 5) are measured and plotted as a frequency histogram.
The resultant frequency distribution of intercepts length for
the granule shown in Fig. 2a is shown in Fig. 2c. To avoid
double counting, the distance D between probing lines
should be larger than the dimension of the largest pore to
be analyzed. The bin width on the plot is typically constant
and is chosen to permit each bin to accumulate enough
counts for good statistical precision. Enough bins should be
chosen to show the shape of the distribution. To improve
statistics, data from several cross-sections (with the distance
between them larger than the diameter of the largest pore)
should be combined. Assuming that the channels and
chambers on the image (see Fig. 2b and the description in
the text) can be represented as equivalent spheres, the size
distribution of such spheres can be unfolded following the
procedure described in details in Ref. [8]. An example of a
distribution of such equivalent spheres unfolded from Fig.
Fig. 5. Application of linear intercepts method for analysis of open porosity
in granule HS. A grid of three straight lines (L1 – L3) is superimposed over
a cross-sectional image of Fig. 2b. Lij intercept; D-spacing between probing
lines.
2c is presented in Fig. 2d. Typical overall intercepts counts
should exceed 1000 for good statistical precision.
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