European Journal of Pharmaceutical Sciences 22 (2004) 173179

Inuence of particle size and shape on owability and compactibility of

binary mixtures of paracetamol and microcrystalline cellulose
J. Sebastian Kaerger, Stephen Edge, Robert Price

Pharmaceutical Technology Research Group, Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK
Received 24 September 2003; received in revised form 2 March 2004; accepted 9 March 2004
Abstract
The inuence of the size andshape of paracetamol particles onthe owandcompressionbehavior of blends (1:1) of microcrystalline cellulose
(MCC) was investigated. The effect of paracetamol particle shape was investigated by using two differently prepared samples, micronized
and novel engineered Solution Atomization and Xstallization by Sonication (SAXS) particles, which exhibited similar particle size ranges
(26 m). The results were compared to data obtained for an untreated paracetamol sample. The blends containing SAXS particles exhibited
increased bulk and tapped density and improved ow, compared to the blend containing micronized particles. This may reect differences
in shape since the SAXS particles exhibited spherical morphology. The compressibility of the blend containing untreated paracetamol was
greater than blends containing the SAXS and micronized materials, which may reect the different drug particle sizes and shapes. However,
blends containing the needle-shaped particles of pure untreated sample, exhibited poor compactibility after storage at 10% RH. It was found
that increasing the moisture content in the blends by storage at 44% RH resulted in an increase in the compactibility of the samples containing
untreated and SAXS paracetamol with the blends containing micronized paracetamol being relatively unaffected. In general, tablets prepared
fromblends containing smaller particles of paracetamol exhibited signicantly greater compactibility compared to tablets prepared containing
the larger particle sized untreated paracetamol. The use of small, spherical drug particles may result in improvements in the bulk density,
densication and compactibility of blends of paracetamol and microcrystalline cellulose.
2004 Elsevier B.V. All rights reserved.
Keywords: Paracetamol; Binary mixture; Particle shape; Compactibility; SAXS
1. Introduction
Even though paracetamol is a poorly compactable drug it
is still widely used in a solid dosage forms for its analgesic
and antipyretic properties. In terms of tablet formation, the
specications of a nished tablet will be a consequence
of the compressibility, adhesive/cohesive interactions and
mechanical properties of the component particles. Con-
sequently, a poorly compactable drug may result in for-
mulation difculties. The poor compaction behavior of
paracetamol has been explained in terms of the crystal
structure of the material, which is based on a monoclinic
crystal system, and its poor plastic deformation (Nichols
and Frampton, 1998; Beyer et al., 2001). In order to address

Corresponding author. Tel.: +44-1225-383644;

fax: +44-1225-386114.
E-mail address: r.price@bath.ac.uk (R. Price).
this problem the crystal structure has been modied by rapid
cooling of a paracetamol melt, resulting in an orthorhombic
system. This material has also been prepared by crystal-
lization from organic solvents such as benzyl alcohol and
methylated spirits (Nichols and Frampton, 1998). This ma-
terial exhibited improved compactibility. However, its crys-
tal structure is thermodynamically unstable and so far only
relatively small amounts have been produced (DiMartino
et al., 1996; Sacchetti, 2000). More recently, higher yields
of orthorhombic paracetamol have been prepared by crystal-
lization from ethanolic solution (Al-Zoubi and Malamatris,
2003). Garekani et al. attempted to improve the poor
compaction properties of paracetamol by modifying the
crystal shape by employing polyvinylpyrrolidone (PVP)
as a crystal growth inhibitor (Garekani et al., 2000a,b).
The resulting particles exhibited improved compression
properties. However, the degree to which PVP inuences
the compression behavior was not determined even though
0928-0987/$ see front matter 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.ejps.2004.03.005
174 J.S. Kaerger et al. / European Journal of Pharmaceutical Sciences 22 (2004) 173179
the amount of PVP in the collected material was 44.5%
(w/w).
In view of the poor ow properties of paracetamol, the
active can be granulated before compression (Rasenack
and Mller, 2002). Nevertheless, in order to avoid the
time-consuming and expensive granulation process it may
be possible to produce an optimal blend of excipients and
drug which could afford formulations with improved com-
pressibility and compactibility in direct compression. Many
studies of powder mixtures have described the relationships
between particle size and ratio of excipients and drug and
tablet strength (Fell, 1996; Kuentz and Leuenberger, 2000;
Alderborn, 1996). However, the relationship between tablet
strength and the particle sizes in a binary mixture has been
rarely studied (Malamataris et al., 1984). In view of this,
the effect of particle shape on the compactibility of pure
drug has been reported (Alderborn and Nystrom, 1982;
Karehill et al., 1990; Wong and Pilpel, 1990). Adolfsson
et al. (1998) studied pure material and blends of drug and
binder, microcrystalline cellulose (MCC), to explore the in-
uence of surface roughness and molecular disorder on the
compactibility and the contribution of weak distance forces
and solid bridges to the tensile strength of resulting tablets.
The drug particles used were much larger (250355 m)
than the MCC particles (20 m).
The inuence of moisture on the compaction behavior of
MCC, blends of MCC with different drugs and paraceta-
mol has been extensively studied (Khan et al., 1981; Garr
and Rubinstein, 1992; Amidon and Houghton, 1995;
Bolhuis and Chowhan, 1996). These studies concluded that
increasing the water content of MCC results in an increase
in the compactibility. This was explained in terms of lubri-
cation effects of moisture and its ability to facilitate slippage
of the MCC brils. It would be expected that there would
be an optimum amount of water which will limit elastic
recovery after compression by the formation of hydrogen
bond bridges (Khan et al., 1981; Bolhuis and Chowhan,
1996). However, the wide range of studies of the effect of
moisture on the compaction of MCC and blends of MCC
has resulted in a variety of relationships which are difcult
to fully interpret (compression pressure, compression speed,
direction of compression, dwell time, decompression rate,
storage, RH, excipient manufacturer, etc.). Nevertheless,
these studies generally agree that the compressibility of
MCC is closely related to the amount of water in MCC or in
the blend at water contents above 5% (w/w). However, data
obtained for MCC with water contents below 5% (w/w)
have been difcult to fully explain. For example, Khan
et al. reported no signicant dependence on water content
for pure MCC at low compaction pressure (Khan et al.,
1981). Conversely, in blends of MCC and paracetamol, it
was suggested that there was an inuence of water content
at low compaction pressure (Amidon and Houghton, 1995;
Akande et al., 1997; Malamataris et al., 1984, 1996).
The object of this work was to investigate the relation-
ship between owability, compressiblity and compactibility
in blends of paracetamol particles of different sizes and
shapes with MCC at different water contents. Paracetamol
was employed as three different sizes and shapes: as sup-
plied (particle size ca. 40 m, needle shaped), micronized
(particle size between ca. 2 and 6 m, unevenly shaped)
and produced by a novel particle engineering method (Solu-
tion Atomization and Xstallization by SonicationSAXS;
particle size between ca. 2 and 6 m, spherically shaped).
2. Materials and methods
2.1. Materials
Paracetamol (Sigma-Aldrich, Steinheim, Germany),
ethanol, cyclohexane (HPLC grade), magnesium stearate
(all supplied by Fisher Chemicals, Loughborough, UK), mi-
crocrystalline cellulose (Emcocel 90M, Lot-Nr. E9B8A01X
Penwest, Patterson, USA) and talc (BDH, Poole, UK) were
used as supplied.
2.2. Production of paracetamol samples
Paracetamol samples were prepared using two techni-
ques.
2.2.1. Novel particle engineering method
The SAXS process has been previously described
(Kaerger and Price, 2004) and the system is diagramatically
represented in Fig. 1. Simply, a solution of paracetamol
in ethanol (10%, w/w) was sprayed (16 ml/h) using an air
pressure atomizer (orice 0.7 mm, air ow 600 l/h). After
evaporation of the solvent the supersaturated droplets were
collected in a non-solvent, cyclohexane. Crystallization of
the drug within the droplets was achieved using an ultra-
sonic source (FS200b, Decon Laboratories, Hove, UK). The
resulting suspension was ltered through a membrane lter
Fig. 1. Schematic diagram of the apparatus employed to obtain spherical
particles by Solution Atomization and Xstallization by Sonication (SAXS).
J.S. Kaerger et al. / European Journal of Pharmaceutical Sciences 22 (2004) 173179 175
(Isopore membrane lter 0.2 (m GTBP, Millipore, UK) and
the particles dried for 100 min at 50

C.
2.2.2. Micronization
Paracetamol was micronized using a centrifuge mill
(ZM100, Rentsch, Haan, Germany). The centrifugal speed
was set at 18,000 rpm with a 80 m sieve.
2.3. Preparation of powder blends
All blends were prepared using paracetamol (49.25%,
untreated, micronized and SAXS-produced paracetamol),
MCC (49.25%), talc (1%) and magnesium stearate (0.5%).
Required mass of drug, MCC and talc (total, 5 g) were
mixed for 5 min in a Turbula mixer in a 50 ml glass cylinder
(46 rpm, Willy A. Bachofen AG, Basel, Switzerland). Mag-
nesium stearate was then added and the blends were mixed
for a further 5 min. The resulting formulations were stored
for 5 h at 65

C to ensure crystallization. The blends were

then either stored over silica gel in a desiccator (10% RH)
or at 44% RH (saturated solution of K
2
CO
3
in water, in a
hermetically sealed enclosure) at 21

C for at least 7 days

prior to use.
2.4. Physical characterization
2.4.1. Scanning electron microscopy (SEM)
The morphology of the paracetamol particles was investi-
gated using scanning electron microscopy (SEM) (Jeol 6310,
Jeol, Japan) at 10 keV. Samples were mounted on carbon
sticky tabs and gold-coated prior to analysis (Edwards Sput-
ter Coater, UK).
2.4.2. Particle size analysis
Particle size distributions were determined by laser
diffraction (Mastersizer X, Malvern, UK), using a 100 mm
lens in a small stirring cell (volume 10 ml) with an obscu-
rity between 0.12 and 0.18. A small amount of drug was
dispersed in cyclohexane with 0.1% lecithin as surfactant.
The suspension was sonicated for 5 min (FS200b, Decon
Laboratories, Hove, UK) prior to analysis.
2.4.3. Differential scanning calorimetry (DSC)
Thermal analysis (35 mg) was performed using a dif-
ferential scanning calorimeter (DSC2910, TA Instruments,
USA) using hermetically sealed aluminium pans. The sam-
ples were cooled to 70

C and heated to 300

C at a rate
of 10

C/min.
2.4.4. Surface area measurement
Surface areas were determined using helium/nitrogen gas
sorption (Gemini 2360 Surface Area Analyzer, Micromet-
rics, Norcross, USA). Prior to measurements, samples (0.8 g)
were degassed for 15 h to remove moisture and contami-
nation (FlowPrep 060, Micrometrics, Norcross, USA). The
surface area was calculated by employing the adsorption
theories of Brunauer, Emmett and Teller (BET) (Brunauer
et al., 1938), and Langmuir (Langmuir, 1918).
2.4.5. Water content
The water content of samples was determined by heat-
ing the powders (2 g) at 105

C (Mettler IR-heater LP16

with balance PM2500) until the sample achieved constant
mass. The mass difference was considered as the water
content.
2.4.6. Bulk and tapped density
The bulk density of blends was determined by pouring
a sample of the powder (2 g) into a 10 ml measuring glass
cylinder and measuring the powder volume. The tap density
was determined after tapping the cylinder using a jolting
volumeter (J. Engelsmann, Ludwigshafen, Germany). The
powder volume was measured after successive 500 tap cy-
cles until the volume was constant and the tapped density de-
termined. Carrs compressibility index was calculated from
the bulk and tapped densities (Carr, 1965).
2.4.7. Flowability
The owability was determined by measuring the angle
of repose. The end of a funnel was placed 2 cm above a
at base. Powder (the mass depended on the bulk density of
the material, around 2.5 g) was lled into the funnel, so that
after releasing the powder out of the funnel the top of the
resulting cone reached the end of the funnel. The powder
was released from the funnel. From the height of the cone
(h) and the diameter at the base (d) the angle at the base,
the angle of repose, () was determined.
tan =
2h
d
(1)
2.5. Powder compression and compaction
Tablets of the blends (250 mg, 10 mmdiameter, silver steel
dies) were prepared using a computer controlled texture an-
alyzer (TA-XT2i, Stable Micro Systems, Godalming, UK).
Before each compression the die and the punch faces were
lubricated with a magnesium stearate suspension (acetone).
The powder was added into the die and the die gently tapped
ve times. Tablets were prepared at compression and decom-
pression speeds of 5 mm/s at 62.4 MPa (4905 N, dwell time
1 s). The compressibility, in millimeters, was in this case, de-
ned as the die travel distance from 0.13 MPa (10 N) to the
maximum load. In this case, the greater the compressibility,
the greater the resistance to the applied stress. The tablets
were stored at 44% RH for 24 h before mechanical testing.
The density was calculated after measurement of the mass,
thickness and diameter of the tablets (Mitutoyo Micrometer,
Tokyo, Japan). The compactibility was determined by dia-
metric compression testing (0.17 mm/s, silver steel platens,
Texture Analyzer, Stable Micro Systems, Godalming, UK).
The failure load was converted to tensile strength (Fell and
Newton, 1970).
176 J.S. Kaerger et al. / European Journal of Pharmaceutical Sciences 22 (2004) 173179
3. Results and discussion
3.1. Production and characterization of paracetamol
particles
In order to investigate the inuence of paracetamol par-
ticle shape and size on the properties of paracetamol/MCC
blends, two relatively small particle sized paracetamol sam-
ples were prepared by two different methods, micronization
and a novel particle engineering technique technique. The
properties of these materials were compared with unmodi-
ed paracetamol.
Fig. 2. Scanning electron micrographs of (a) untreated, (b) micronized,
(c) SAXS paracetamol.
Fig. 3. Size distribution of untreated, micronized and SAXS-processed
paracetamol particles.
3.2. Characterization of paracetamol particles
3.2.1. SEM
Representative SEM micrographs of the unmodied,
milled and SAXS paracetamol particles are shown in Fig. 2.
The SEM micrographs suggest that milling and SAXS pro-
cessing produce relatively small sized paracetamol particles.
However, the samples produced by the SAXS process are,
as expected, more spherical in appearance compared to the
milled samples.
3.2.2. Particle size analysis
The particle size distributions of the three paraceta-
mol samples are represented in Fig. 3. As expected, the
SAXS-processed and the micronized samples exhibit sim-
ilar but smaller particle sizes compared to the unmodied,
as supplied, sample.
3.2.3. DSC
The DSC thermograms of the untreated, micronized and
SAXS-processed paracetamol samples are shown in Fig. 4.
The DSC melting point (T
m
) was used to identify the crys-
talline form of paracetamol present, monoclinic (form I, T
m
Fig. 4. DSC thermograph of paracetamol particles, untreated, micronized
and obtained by SAXS.
J.S. Kaerger et al. / European Journal of Pharmaceutical Sciences 22 (2004) 173179 177
Table 1
Experimental values of the surface area of single drug and binary mixtures
Drug Surface area (m
2
/g) Surface area of
the blend (m
2
/g)
MCC 1.24
Untreated paracetamol 0.18 0.62
Micronized paracetamol 2.13 1.42
SAXS paracetamol 1.70 1.23
= 169

C) and the orthorombic form (form II, T

m
= 156

C)
(Nichols and Frampton, 1998). Untreated paracetamol was
supplied in form I. The data in Fig. 4 show endothermic tran-
sitions at ca. 169

C for all samples. These correspond to the

melting point of form I. No thermal transition was observed
at 156

C, the melting point of form II. Furthermore, the ab-

sence of an exothermic recrystallization event, at 76

C, in-
dicates the absence of amorphous material (DiMartino et al.,
1996). The heat of fusion at T
m
was determined as 1985 J/g
for all three particle samples, which suggests that no degra-
dation has taken place.
3.3. Preparation and characterization of the blend
Samples of untreated, micronized and SAXS produced
paracetamol were blended with MCC, talc and Mg stearate.
The resulting formulations were uniform in appearance.
The surface areas of the resulting blends were determined.
The results are presented in Table 1 and suggest that, as ex-
pected, a reduction in particle size of paracetamol results in
an increase in surface area. Consequently, blends containing
processed paracetamol samples exhibit higher surface areas
than the blend prepared containing unmodied paracetamol.
The owability data for the blends are shown in Table 2.
The data suggest that blends containing untreated and SAXS
produced paracetamol exhibit similar bulk and tapped den-
sity, whereas the blend containing micronized drug exhibits
lower bulk and tapped density. The Carrs compressibility in-
dex of the blends containing micronized paracetamol (stored
at both 10 and 44% RH) is also signicantly higher than for
the blends containing SAXS-processed and untreated parac-
etamol (ANOVA, P < 0.05). However, these values together
with the relatively high angles of repose, suggest that these
blends exhibit relatively poor ow. The effect when using
micronized paracetamol may be explained in terms of the
Table 2
Experimental values of owability, density and water content of each blend
Paracetamol type Storage (% RH) Angle of repose (

) Bulk density (g/cm

3
) Tapped density (g/cm
3
) Carrs index Water content (%, w/w)
Untreated 10 50 1 0.34 0.01 0.54 0.01 38 2 0.9
Micronized 10 52 1 0.21 0.01 0.40 0.01 47 1 0.9
SAXS 10 49 1 0.33 0.01 0.53 0.01 37 2 1.1
Untreated 44 48 1 0.34 0.01 0.56 0.01 39 1 2.2
Micronized 44 51 1 0.20 0.01 0.36 0.02 45 3 2.3
SAXS 44 48 1 0.31 0.01 0.50 0.01 38 1 2.3
Results are the mean and standard deviations of three determinations.
materials uneven morphology and consequent higher sur-
face/volume ratio. This would be expected to inhibit ow
due to the increased number of inter-particulate interactions
at both macroscopic (mechanical) and microscopic (van der
Waals) levels. This may also reect surface properties of the
micronized material, since micronized materials are known
to show higher electrostatic forces due to triboelectrica-
tion during the milling process. This effect is reduced when
blends are prepared using the spherically shaped SAXS par-
ticles which would be expected to impart improved ow due
to their shape and lower surface free energy, as exemplied
by the previously mentioned tapped and bulk density data.
The water content of each blend is shown in Table 2. Typ-
ically, the amount of water in the blends was ca. 1% (w/w)
and 2.3% (w/w) after storage at 10 and 44% RH, respec-
tively. This is in agreement with a previous study (Amidon
and Houghton, 1995). The majority of the moisture uptake
during storage is due to MCC since paracetamol adsorbs
only up to 0.1% water between 0 and 90% RH as deter-
mined by dynamic vapor sorption (results not shown). The
inuence of the moisture on bulk properties of the blends
is shown in Table 2. No statistically signicant difference
was found (ANOVA, P < 0.05) between the tapped and
bulk densities of the blends after storage at 10 and 44% RH
suggesting that the density and ow characteristics of these
blends is not signicantly affected at these water contents.
3.4. Mechanical behavior of blends
3.4.1. Compressibility
Typical compression data of the blends, after storage at
10% RH, are shown in Table 3. The data suggest that when
blended with paracetamol, the order of blend compressibil-
ity is, as expected, untreated > milled > SAXS-processed
after storage at 10 and 44% RH. The greater compressibility
of the blend containing the untreated paracetamol proba-
bly reects the larger particle size of these drug particles
which, because of their shape and relative brittleness offer
more resistance to compression. In the case of the blends
containing the smaller particle sized paracetamol samples,
the presence of the SAXS-processed paracetamol facilitates
rearrangement of the powder column at low stress resulting
in a blend which is apparently less compressible than the
blend containing the micronized drug. This is also reected
in the bulk density data where blends containing SAXS and
178 J.S. Kaerger et al. / European Journal of Pharmaceutical Sciences 22 (2004) 173179
Table 3
Compression values of 250 mg blend and characterization of resulting tablets, compressed at 62.4 0.4 MPa (at punch face, diameter 10 mm, silver
steel dies)
Paracetamol type Storage (% RH) C (mm) E
c
(J) D
t=0
(g/cm
3
) D
t=24
(g/cm
3
)
a
Tensile strength (MPa) NE
f
(J/m
2
)
Untreated 10 4.21 0.05 4.85 0.07 1.07 0.01 1.05 0.01 0.35 0.05 21.4 1.4
Micronized 10 4.04 0.12 4.32 0.08 1.04 0.01 1.03 0.01 0.65 0.09 36.0 7.9
SAXS 10 3.77 0.06 4.48 0.07 1.07 0.01 1.06 0.01 0.59 0.12 33.7 4.2
Untreated 44 4.23 0.07 4.81 0.07 1.12 0.01 1.10 0.01 0.56 0.05 29.5 3.0
Micronized 44 4.05 0.04 4.53 0.13 1.07 0.01 1.05 0.01 0.65 0.07 40.9 7.7
SAXS 44 3.79 0.11 4.64 0.15 1.10 0.01 1.08 0.01 0.70 0.06 35.9 8.1
a
C: compressibility; E
c
: energy of compression; D
t =0
: density after ejection; D
t =24
: density after storage at 44% RH, 24 h; NE
f
: normalized energy
of failure during diametric compression test. Results are the mean and standard deviations of six determinations.
untreated paracetamol exhibit similar bulk densities, but
different compressibilities, and the energy of compression
data in Table 3 where it can be seen that even though there
is no effect on the compressibility of the blends after stor-
age at 10 and 44% RH, there is an increase in the energy
of compression for the blends containing the micronized
and SAXS-processed paracetamol samples. The increase in
the energy of compression reects water induced increased
elastic/plastic behavior. It has been reported that the com-
pression of MCC required less pressure with increasing
moisture content to produce tablets of identical solid frac-
tion (Amidon and Houghton, 1995). The fact that blends
containing untreated paracetamol require comparable com-
pression energies at 10 and 44% RH suggest that it is the
shape and size of the paracetamol particles which deter-
mines the energy of compression. This observation is also
mirrored in the tablet density data in Table 3 which sug-
gests that blends containing untreated and SAXS-processed
paracetamol exhibit comparable ejected tablet densities
which are greater than the tablets prepared from the blend
containing micronized drug (ANOVA, P < 0.05).
Overall, the compressibility data in Table 3 suggest that,
in the case of small particles of paracetamol, the energy of
compression of the blends is dependant on moisture con-
tent rather than apparent compressibility. However, the blend
containing micronized sample is more compressible than the
blend containing SAXS-processed paracetamol and affords
tablets with lower density suggesting that particle process-
ing and shape determine the apparent mechanical properties
such as compressibility and compactibility. This difference
in behavior of the blend containing the micronized sample is
also reected in the Carrs compressibility data in Table 2,
where the blend containing the micronized drug exhibits
lowest bulk and tapped density.
3.4.2. Compactibility
The tensile strengths of tablets are reported in Table 3.
After storage at 10% RH, the blends containing untreated
paracetamol produced tablets which exhibited lower tensile
strength than those containing the smaller particle sized
drugs (ANOVA, P < 0.05). There was no signicant dif-
ference in the tensile strengths of the tablets containing
SAXS-processed and micronized drug (P > 0.05). The
compactibility increased after storage at 44% RH for blends
containing untreated and SAXS-processed paracetamol
(ANOVA, P < 0.05). However, the results seem to suggest
that the inuence of humidity on the compactibility of the
blends is untreated > SAXS-processed > micronized. A
possible explanation is that the hydration of the surface
of the paracetamol crystals is now sufcient to offer some
bonding capacity which is reected in the increased tablet
densities. This is not the case for the blend containing
the micronized drug where there is no apparent change in
the compactibility suggesting that the inherent properties
of the micronized drug have a strong inuence on com-
paction. Tablets containing small particles of drug exhibited
greater tensile strength at low moisture content (ANOVA,
P < 0.05) compared to untreated particles, whereas at 44%
RH the probability of similarity was greater than 5%.
3.5. Conclusions
Three types of paracetamol powder were blended with
MCC, untreated paracetamol and two small particle sized
samples, one micronized and one SAXS-processed. The
blends containing the SAXS particles exhibited bulk and
tapped densities and Carrs indices which were similar to
the blend containing untreated larger particle sized paraceta-
mol, but greater density and smaller Carrs index than those
containing micronized paracetamol, after storage at 10 and
44% RH. The Carrs index of all the blends suggested the
formulations would exhibit relatively poor ow.
The tensile strengths of tablets of blends of MCC and
both the small paracetamol particles were greater than
for a blend containing untreated paracetamol after storage
at 10% RH. An increase in moisture content resulted in
greater compactibility of the blends containing untreated
and SAXS-processed paracetamol suggesting that the pro-
cessing history of paracetamol may affect its tableting func-
tionality. For blends containing untreated paracetamol, there
was no increase in the energy of compression after storage
at 44% RH suggesting that it is the shape, and consequent
brittleness of the drug crystals which affects compression
energy rather than a moisture induced increase in the com-
pressibility of MCC. However, the effect of humidity when
increased from 10 to 44% RH on compactibility appeared
J.S. Kaerger et al. / European Journal of Pharmaceutical Sciences 22 (2004) 173179 179
to be greater for blends with pure untreated paracetamol
compared with blends containing processed material.
Overall, blends of MCC and SAXS-processed parac-
etamol exhibited comparable ow and improved tableting
functionality to blends containing large sized untreated
paracetamol. The use of a miconized paracetamol in
the production of blends with MCC produced powders
which exhibited poorer ow than blends prepared with a
comparably sized SAXS-processed material. The use of
SAXS-processed drugs may afford formulations with im-
proved ow and tableting functionality. Investigations are
underway further investigating the effect of these smaller
particle sized drugs powder and tableting functionality and
on dissolution of poorly soluble drugs.
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