International Journal of Pharmaceutics 441 (2013) 527534

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International Journal of Pharmaceutics

journal homepage: www.elsevier.com/locate/ijpharm

Flow and compaction behaviour of ultrane coated ibuprofen

Parth K. More, Kailas S. Khomane, Arvind K. Bansal
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Mohali, Punjab, India

a r t i c l e

i n f o

Article history:
Received 23 August 2012
Received in revised form 30 October 2012
Accepted 31 October 2012
Available online 8 November 2012
Keywords:
Compaction
Dry coating
Ibuprofen
Tableting
Mechanical properties
Super plasticity
Compression
Crushing strength

a b s t r a c t
Good ow and compaction properties are prerequisites for successful compaction process. Apart from
initial prole, mechanical properties of pharmaceutical powders can get modied during unit processes
like milling. Milled powders can exhibit a wide range of particle size distribution. Further downstream
processing steps like compaction can be affected by this differential particle size distribution. This has
greatest implications for formulations like high dose drugs wherein the active pharmaceutical ingredient
(API) contributes the maximum bulk in the nal formulation. The present study assesses the impact of
dry coating with ultrane particles of same material, on the ow and compaction properties of the core
material. Ibuprofen was selected as model drug as it has been reported to have poor mechanical properties. Ultrane ibuprofen (average size 1.75 m) was generated by Dyno milling and was dry coated
onto the core ibuprofen particles (average size 180 m). Compaction studies were performed using a
fully instrumented rotary tablet press. Compaction data was analyzed for compressibility, tabletability,
compactibility proles and Heckel plot. Dry coating of the ibuprofen exhibited greater compressibility and tabletability, at lower compaction pressure. However, at compaction pressure above 220 MPa,
compressibility and tabletability of coated as well as uncoated materials were found to be similar. Heckel
analysis also supported the above ndings, as Py value of uncoated ibuprofen was found to be 229.49 MPa
and for 2.0% ultrane coated ibuprofen was found to be 158.53 MPa. Lower Py value of ultrane coated
ibuprofen indicated ease of plastic deformation. Superior compressibility and deformation behaviour of
ultrane coated ibuprofen attributed to increased interparticulate bonding area. This strategy can also
be explored for improving tabletability of high dose poorly compressible drugs.
2012 Elsevier B.V. All rights reserved.

1. Introduction
Tablet is the most preferred dosage form to orally deliver drugs,
as it offers numerous technical and economical advantages (Han
et al., 2008; Patel et al., 2006). However, poor mechanical properties
become a hurdle in successful development of tablet formulation.
This becomes severe in case of high dose poorly compressible drugs
like ibuprofen. Moreover, mechanical properties of pharmaceutical
powders can modify during unit processes like milling. Milling can
generate ultrane or nano particles that can get coated onto the
bigger core particles and affect the mechanical properties like ow
and compressibility. This may have profound impact in case of high
dose poorly compressible drug. Hence it is imperative to study the
effect of ultrane coating on the mechanical properties of high dose
poorly compressible drug.
Various approaches have been reported to improve the mechanical properties of the material. Crystal habit modication by

Corresponding author at: Department of Pharmaceutics, National Institute of

Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Mohali, Punjab 160
062, India. Tel.: +91 172 2214682 2126; fax: +91 172 2214692.
E-mail address: akbansal@niper.ac.in (A.K. Bansal).
0378-5173/$ see front matter 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.ijpharm.2012.10.048

crystallization from different solvents was reported as an aid to

improve the densication behaviour of nitrofurantoin (Marshall
and York, 1991). Bacher et al., showed improved compactibility
and compressibility of calcium carbonate and sorbitol using wet
granulation (Bacher et al., 2008). The effect of particle size and compaction force on the compaction behaviour of paracetamol was also
studied (Patel et al., 2007). Co-crystallization of caffeine also led to
improvement in the mechanical properties (Sun and Hou, 2008).
Recently, modication of the surface by coating, has been reported
to improve the ow (Hou and Sun, 2008; Jallo et al., 2011; Yang
et al., 2005) and compaction properties (Shi and Sun, 2011) of a
material. When the materials blended, differ largely in their particle
sizes, the smaller material tend to coat on the coarser material. The
adhering material tends to form a percolating network which governs the compaction properties of the material (Barra et al., 1999).
Mechanical properties of the guest material critically contribute
to these changes. It was demonstrated that poorly bonding guest
material improves the ow properties, but deteriorates the compaction properties (Sun, 2011). For example, dry coating of colloidal
silica (Cab-O-Sil) on the MCC particles improved ow property but
reduced the tabletability (Chattoraj et al., 2011). Improvement in
the ow property was attributed to reduced interaction/bonding
between the particles and ball bearing effect. However,

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deterioration of the compaction properties was attributed to reduction in the bonding strength of the material due to presence of
poorly bonding silica on the surface of MCC.
It has also been reported that coating of an API with highly bonding polymers like PVP improved tableting properties (Shi and Sun,
1999). All the reported examples employed coating of a different
guest material on the core material and bonding strength played
a crucial role in governing the compaction behaviour. However, a
report dealing with coating of the ultrane particles (particles having size below 15 m) of the same material and its impact on ow
and compaction is still lacking.
Present study assesses impact of coating of ultrane particles
of same material on the ow and compaction properties of the
core material. Ibuprofen was selected as model drug. Ultrane particles of ibuprofen (average size 1.75 m) were generated using
Dyno mill and coated onto core material of average particle size
of 180 m, by dry coating method. Compaction behaviour was
assessed using a fully instrumented rotary tablet press and data
was analyzed for compressibility, tabletability, compactibility prole (CTC prole) and Heckel plot. This science based approach helps
to understand the effect of material properties on the processability
of tablets in the perspective of QbD principles (Yu, 2008).
2. Experimental
2.1. Materials
2.1.1. Ibuprofen
Ibuprofen was kindly gifted by Arbro Pharmaceuticals Ltd., New
Delhi, India. Sample exhibited plate shaped crystal habit. It was
passed through set of sieves and the fraction BSS # 6080 was used
as ibuprofen core/bulk material (IBU).
2.2. Methods
2.2.1. Generation of ultrane ibuprofen (UIBU)
Wet milling process was used to generate ultrane IBU. 10 g of
IBU and 100 ml of distilled water was introduced into the milling
chamber. Twice volume (200 ml) of glass beads of 0.751 mm size
was added to it. IBU was subjected to wet milling using Dyno mill
(Willy A. Bachofen AG Maschinenfabrik, Basel, Switzerland) for 1 h.
Temperature of the milling chamber was maintained at 4.0 0.2 C
during the milling process. Average particle size of IBU ultrane
suspension was determined using Zeta sizer (Nano ZS, Malvern,
Worcestershire, UK). Ultrane suspension obtained by the milling
process was dried overnight at 60 C in a vacuum oven (Narang Scientic Works Pvt Ltd., New Delhi, India). The agglomerated material
obtained upon drying was milled using mortar pestle and passed
through BSS # 200 to get loose aggregates of ultrane IBU (UIBU).
2.2.2. Coating of UIBU on core particles (IBU)
Initially, UIBU and IBU were geometrically mixed. The mixture (10 g) was poured into a plastic bottle and 20 g of glass
beads (45 mm size) were added to it. The method was optimized
for the ratio of glass beads to IBU (1:1, 2:1, 3:1) and processing
time (10 min, 20 min, 30 min). The bottle was attached to horizontally mounted shaft of Kalweka instrument (HD 410 E, Kalweka,
Gujarat, India) and rotated at 150 rpm. Different percentages of
ultrane coatings were applied to obtain ultrane coated IBU
(UCIBU). A control (DCC) sample was generated by processing IBU
under similar conditions of amount of glass beads and processing
time, but without adding UIBU.
2.2.3. Solid state characterization
PXRD patterns of IBU, UIBU and 2.0% UCIBU were recorded at
room temperature on Brukers D8 Advance diffractometer (Bruker

at
AXS, Karlsruhe, West Germany) with Cu K radiation (1.54 A),
40 kV, 40 mA passing through nickel lter. Analysis was performed
in a continuous mode with a step size of 0.01 and step time of 1 s
over an angular range of 340 2. Obtained diffractograms were
analyzed using DIFFRACplus EVA (Version 9.0) diffraction software
(Bruker AXS, Karlsruhe, West Germany).
Differential scanning calorimetry (DSC) of IBU, UIBU and 2.0%
UCIBU was conducted using DSC, Model Q2000 (TA Instruments,
New Castle, USA). Prior to analysis, the instrument was calibrated
using high purity standard of Indium for temperature and heat ow
measurement, respectively. DSC cell was purged with 50 ml/min
dry nitrogen. Accurately weighed samples (12 mg) were heated in
standard aluminium pans in the temperature range of 25 to 100 C,
using a heating rate of 10 C/min. Low temperature DSC of UIBU was
carried out in the temperature range of 60 to 25 C to rule out
the possibility amorphization during milling. Obtained data was
analyzed using the software Universal Analysis (TA Instruments,
New Castle, USA).
Hot stage microscopy (HSM) of IBU, UIBU and 2.0% UCIBU
was carried out using Leica DMLP polarized microscope (Leica
Microsystems, Wetzlar, Germany) equipped with Linkam LTS
350 hot stage (Leica Microsystems, Wetzlar, Germany). Samples were mounted on the glass slide and heated from 25 to
80 C at the heating rate of 5 C. Photographs were taken using
JVS colour video camera and analyzed using Linksys32 software.
Additionally, optical and polarized microscopy of IBU, UIBU and
2.0% UCIBU were performed by mounting them on glass slides
and observing them under optical as well as polarized light
mode.
Particle size distribution of DCC and UCIBU samples was
determined microscopically by measuring diameter along the
longest axis (DMLP polarized microscope, Leica Microsystems, Wetzlar, Germany). Moisture content (n = 3) of DCC and
UCIBU samples was determined by Karl Fischer (KF) titration
(Metrohm 794 Basic Titrino, Herisau, Switzerland). Instrument
was calibrated with disodium tartrate dihydrate for accurate moisture determination. Sample size of approximately
200 mg was utilized for the moisture content determination.
Scanning electron microscopy (SEM) of UIBU, DCC and 2.0%
UCIBU was performed using a scanning electron microscope (S3400, Hitachi Ltd., Tokyo, Japan) operated at an excitation voltage
of 10 kV at different magnications. Powders were mounted onto
steel stage using double sided adhesive tape and coated with gold
using ion sputter (E-1010, Hitachi Ltd., Tokyo, Japan).
2.2.4. True density and ow properties
True density (n = 3) of IBU was determined by helium pycnometer/true density metre (Pycno 30, Smart Instruments, Mumbai,
India). Bulk density (n = 3) of DCC and UCIBU samples was determined using a 100 ml measuring cylinder. Bulk density of UIBU
(n = 3) was determined using a 10 ml measuring cylinder. Tapped
density (n = 3) of the samples was determined by bulk density apparatus (ETD 1020, Electrolab, Mumbai, India) using USP method I.
Flow properties of the materials were determined by calculating
Hausner ratio and Carrs index.
2.2.5. Compaction properties
2.2.5.1. Hydraulic press. Hydraulic press (Hydraulic Unit Model
3912, Carver Inc., Wabash, USA) was used to perform compaction
study of IBU and UIBU. Tablets of the materials were prepared by
compacting 400 mg of materials up to 35 MPa compaction pressure
in a hydraulic press with a dwell time of 2 s using 13 mm punch die
set. The tablets were further characterized for weight, thickness
and hardness.

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529

2.2.5.2. Instrumented rotary tablet press. Rotary tablet press (Mini

II, Rimek, Ahmedabad, India) was equipped at one of the 8 stations
with 8 mm D-tooling with at punch tip. Feed frame was used for
uniform die lling and blind dies were used at all other positions.
Pre-compression rollers were set out of function. Tablets of each
material were compressed at constant volume. The weight of the
tablet was adjusted to 250 5 mg. The applied compaction force
was controlled by the pressure roller with a hand wheel. Compaction force was initially adjusted to low and increased gradually
to collect data at different compaction pressure. Tableting was performed at the constant speed of 14 rpm. Compaction data were
acquired by portable press analyzerTM (PPA) Version 1.2, Revision
D (Data Acquisition and Analyzing System, PuuMan Oy, Kuopio,
Finland), through an infrared (IR) telemetric device with 16-bit
analogue-to-digital converter (6 kHZ). Analysis of compaction data
was carried out by PPA Analyze software (Version 1.2, Revision D,
PuuMan Oy, Kuopio, Finland) (Khomane et al., 2012).
2.2.6. Determination of tablet tensile strength and porosity
Diameter and thickness of the tablets were measured using
calliper (Mitutoyo America Corporation, Chicago, USA) and their
weights were measured using a digital balance (PM480, Mettler
Toledo AG, Greitensee, Switzerland). The hardness of the tablets
was measured using tablet hardness tester (Erweka, Connecticut,
USA). The tensile strength () of the tablets was calculated by using
Eq. (1).
=

2F
dt

(1)

Here, F is the hardness (N) of the tablet obtained by hardness

tester, d is the diameter and t is the thickness of the tablet. The
density of the tablet was calculated from the weight and volume of
the tablet. The solid fraction of the tablet was calculated by dividing
density of the tablet with true density of IBU. The porosity of the
tablet was calculated from the solid fraction using Eq. (2).
porosity = 1 solid fraction

(2)

Compaction pressure was calculated from the punch face area

and compaction force. The data obtained was interpreted to obtain
CTC prole and Heckle plot. Tabletability is represented by the plot
of tablet tensile strength against compaction pressure (Joiris et al.,
1998). Compressibility is represented by the plot of tablet porosity against compaction pressure (Joiris et al., 1998). Compactibility
is represented by the plot of tablet tensile strength against tablet
porosity (Joiris et al., 1998). Heckel plot is the linear transformation of the parametric force and displacement relationship (Patel
et al., 2010). It is represented by the Plot of ln [1/1D] against compaction pressure where D is the relative density of tablet (tablet
density/true density of powder). Reciprocal transformation of the
slope of the linear portion of the Heckel plot gives mean yield pressure (Py ) (Heckel, 1961).

Fig. 1. Plot of particle size distribution of IBU against glass beads/IBU ratio for
processing time of (a) 10 min, (b) 20 min and (c) 30 min.

3.2. Coating of UIBU on core particles

Dry coating involved breaking down the aggregates of UIBU
and coating them onto IBU. However, the process may also reduce
the initial particle size of IBU. Therefore, process was optimized
with respect to (i) ratio of glass beads: IBU (ii) and processing
time. Particle size distribution of IBU after different processing was
determined using optical microscopy and plotted against the three
different ratios of glass beads: IBU and three different time points,
as shown in Fig. 1.
The maximum ratio and processing time that did not signicantly affect the initial particle size of IBU were selected for dry
coating of UIBU on IBU. Accordingly, glass beads: IBU ratio of 2:1
and 20 min processing time were selected (Fig. 1b). Three different
dry coated batches 0.5% UCIBU, 1.0% UCIBU and 2.0% UCIBU, containing 0.5, 1 and 2.0% of UIBU coating, respectively, were generated
using this optimized method.

3. Results and discussion

3.1. Generation of UIBU
Temperature of the milling chamber was maintained at
4.0 0.2 C to prevent melting or degradation of IBU during the wet
milling process. Average particle size of the ultrane suspension
was found to be 1063 nm (PDI 0.469) by Zetasizer . No stabilizer(s)
was included as it may have altered the compaction properties
of IBU. Drying of ultrane suspension produced aggregates which
were milled using mortar pestle and passed through BSS # 200.
This gave a powder of mean diameter of 1.75 m and a range of
0.53.1 m.

Fig. 2. PXRD overlay of IBU, UIBU and 2.0% UCIBU.

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Table 1
Particle size distribution and moisture content of samples.
Parameter

DCC

0.5% UCIBU

1.0% UCIBU

2.0% UCIBU

Particle size distribution (m)

D50
D90

180
230
0.063 (0.005)

168
214
0.08 (0.010)

175
212
0.09 (0.017)

Moisture content (%)

178
216
0.076 (0.005)

Standard deviations are given in parentheses.

3.3. Solid state characterization

Particle size distribution and moisture content of DCC and UCIBU
are shown in Table 1. Particle size distribution of control (DCC)
and coated materials was found similar. Moisture content of the
materials was found <0.1% (Table 1).
PXRD pattern for IBU, UIBU and 2.0% UCIBU (Fig. 2) showed sharp
peaks and compared well with the reported pattern (Plakkot et al.,
2011). PXRD pattern of UIBU was found similar to IBU indicating no
change in the solid form during wet milling process. However, the
intensity of the peaks decreased probably due to reduced preferred
orientation (Koradia et al., 2004; Roberts et al., 2002; Varasteh et al.,
2009). PXRD pattern of 2.0% UCIBU also compared well with IBU,
thus ruling out any solid form change during the coating process.
DSC traces of IBU, UIBU and 2.0% UCIBU showed sharp melting endotherms that correlated well with its reported values in
the literature (Fig. 3) (Kocbek et al., 2006). IBU showed melting
endotherm at 74.75 C (onset temperature) with an enthalpy of
fusion of 127.9 J/g. UIBU showed melting endotherm at 67.71 C
(onset temperature) with an enthalpy of fusion of 106.5 J/g. UIBU
showed lowering of the melting point and enthalpy of fusion.
Lowering of the enthalpy of fusion may be attributed to amorphization during milling. The low temperature DSC (60 to 25 C)
was carried out to characterize the glass transition temperature of
amorphous UIBU. DSC thermogram showed no endothermic event
around reported glass transition temperature i.e. 42.3 C indicating absence of amorphous content in the given sample (Fig. 4).
Hence in absence of amorphous content, lowering of the melting
point and enthalpy of fusion was attributed to the reduction in
the particle size (Alavi and Thompson, 2006; Eckert et al., 1993;
Puri and Yang, 2007). The 2.0% UCIBU showed melting endotherm
(73.37 C) at a position, almost similar to IBU, with an enthalpy of
fusion of 129.3 J/g.
Thermal events of IBU, UIBU and 2.0% UCIBU were also visualized using HSM and they corroborated ndings of DSC. However,
HSM of 2.0% UCIBU revealed interesting information. As shown in
Fig. 5, ultrane particles showed melting at 73.3 C (Fig. 5c and d),

Fig. 3. DSC overlay of IBU, UIBU and 2.0% UCIBU.

followed by melting of the core IBU particles at 78.5 C (Fig. 5e and

f). This further conrmed coating of UIBU over the surface of IBU.
Optical and polarized microscopy of IBU, UIBU and UCIBU were
performed and polarized microscopy showed birefringence in all
the cases.
SEM images of DCC, 2.0% UCIBU and UIBU were captured at different magnications. DCC crystals exhibited irregular plate shape
habit (Fig. 6a). Surface of the DCC particles was found rough at
the magnication of 1000 (Fig. 6c) and 10,000 (Fig. 6e). The
2.0% UCIBU crystals also exhibited plate shaped habit (Fig. 6b) and
showed presence of ultrane particles on the surface (Fig. 6d and
f). SEM images of UIBU showed particles in the ultrane range
(0.55 m) (Fig. 6g and h). Particle size of the ultrane particles
present on the surface of the IBU particles also determined using
SEM (n = 25). Particle size was found in the range of 0.42.4 m.
3.4. True density and ow properties
True density of IBU was found to be 1.1174 0.0006 g/ml which
correlated well with its reported value (Patel and Bansal, 2011).
UCIBU (0.5, 1.0 and 2.0%) showed marginally lower, while UIBU
showed signicantly lower bulk density, as compared to DCC. A
similar trend was also seen in case of tapped density. Carrs index
and Hausner ratio were evaluated as marker of ow properties.
UIBU showed signicant increase, whereas 0.5, 1.0, 2.0% UCIBU
showed marginal increase in that order (Table 2). Poor ow property of UIBU could be attributed to increased cohesivity, due to
milling.
3.5. Compaction properties
3.5.1. Hydraulic press
Hydraulic press was used to perform compaction study of UIBU
as its poor ow property and limited quantity, prevented study on
a fully instrumented rotary tablet press. CTC and Heckel analysis of
IBU and UIBU were performed using the data obtained after characterization of the tablets. Tabletability of UIBU was found superior
over IBU at all compaction pressures as shown in Fig. 7.

Fig. 4. DSC thermogram of UIBU at low temperature (60 to 25 C).

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531

Fig. 5. HSM of 2.0% UCIBU (a) 32.1 C normal mode, (b) 33.1 C polarized mode, (c) 73.3 C normal mode, (d) 74.0 C polarized mode, (e) 78.5 C normal mode and (f) 78.8 C
polarized mode.

Compressibility of UIBU was also found greater than IBU at all

compaction pressure (Fig. 8). Compactibility prole of both the
materials was found similar. Py values of IBU and UIBU were found
to be 50.54 MPa and 18.98 MPa, respectively.

UCIBU showed signicantly lower Py value than DCC and further a decreasing trend was observed with higher percentage of
coating.
3.6. Impact on ow behaviour

3.5.2. Instrumented rotary tablet press

CTC analysis of DCC, 0.5% UCIBU, 1.0% UCIBU and 2.0% UCIBU was
carried out using the compaction data obtained by instrumented
rotary tablet press. Tabletability is the ability of the material to
be transformed into tablets of sufcient strength upon application of compaction pressure (Joiris et al., 1998). Increasing trend in
the tabletability was obtained upon increasing coating with ultrane particles of IBU (Fig. 9a). Tabletability of DCC and 2.0% UCIBU
was signicantly different (P = 0.004). Better tabletability of UCIBU
was achieved due to improved compressibility over DCC at all the
compaction pressures (Fig. 9b). Higher compressibility indicates
greater tendency of volume reduction upon application of compaction pressure (Joiris et al., 1998). However, above compaction
pressure of 220 MPa, the compressibility and tabletability of DCC
and 2.0% UCIBU were found to be almost similar. Compactibility
is the ability of the material to form tablets of sufcient tensile
strength under the effect of densication (Joiris et al., 1998). Compactibility of DCC and UCIBU were found similar at all compaction
pressure (Fig. 9c). Heckel analysis was also performed using the
compaction data (Fig. 9d). Py value for DCC, 0.5%, 1.0%, and 2.0%
UCIBU was found to be 229.49, 194.12, 168.00 and 158.53 MPa.

Present work demonstrated signicant impact of ultrane coating i.e. coating with ultrane particles (average size 1.75 m), on
the coarser particles (average size 180 m) of the same material
on the mechanical properties of IBU including its ow behaviour.
Flow properties of the coated materials were found different than
control material. Ultrane particles tend to coat on the surface of
bulk particles, as they possess high surface energy (as evident from
the SEM images). Ultrane particles present on the surface formed
a percolating network that enhanced interactions between the particles. This led to increase in the cohesivity of the material (Fig. 10).
Increased Carrs index and Hausner ratio of UCIBU over IBU indicated deterioration of the ow properties that was attributed to
increase in the cohesivity of the material. Moreover, an increasing trend was observed (in both the cases) upon increasing coating
load. This indicated worsening of ow properties upon increasing
coating load, due to formation of a more cohesive and strong percolating network. Cohesive materials tend to form aggregates and
demonstrate poor ow. Such materials are difcult to pack than free
owing materials (Luo et al., 2008). This explains the decreasing
trend of bulk and tapped density of UCIBU, upon increasing % of

Table 2
Bulk and ow properties of materials.
Material

Bulk density

Tapped density

Carrs index

Hausner ratio

DCC
UIBU
0.5% UCIBU
1.0% UCIBU
2.0% UCIBU

0.534 (0.003)
0.308 (0.002)
0.509 (0.007)
0.491 (0.005)
0.467 (0.003)

0.682 (0.005)
0.495 (0.004)
0.678 (0.005)
0.678 (0.003)
0.662 (0.013)

21.621 (0.136)
37.823 (0.181)
24.989 (1.120)
27.500 (0.562)
29.365 (1.375)

1.275 (0.008)
1.608 (0.005)
1.333 (0.020)
1.379 (0.006)
1.416 (0.028)

Standard deviations are given in parentheses.

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Fig. 6. SEM images (a) DCC 300 magnication, (b) 2.0% UCIBU 300 magnication, (c) DCC 1000 magnication, (d) 2.0% UCIBU 1000 magnication, (e) DCC 10,000
magnication, (f) 2.0% UCIBU 10,000 magnication, (g) UIBU 6000 magnication and (h) UIBU 15,000 magnication.

Fig. 7. Tabletability of IBU and UIBU.

Fig. 8. Compressibility of IBU and UIBU.

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533

Fig. 9. Compaction data analysis of DCC, 0.5% UCIBU, 1.0% UCIBU and 2.0% UCIBU (a) tabletability plot, (b) compressibility plot, (c) compactibility plot and (d) heckel plot.

coating. Hence, dry coating with ultrane particles, slightly deteriorated the ow properties of IBU.
3.7. Impact on compaction behaviour
Tabletability of the material is governed by its compressibility
and compactibility. Compressibility is dependent on the available
bonding area, while compactibility is dependent on the bonding
strength of the material (Sun, 2011). Modication of the surface,
like coating, may change any of the above property (Shi and Sun,
2011; Yang et al., 2005). Tabletability of UIBU was found to be
superior over IBU, due to its better compressibility. Ultrane particles enhanced the overall bonding area thus facilitating plastic
deformation and compressibility. Findings from Heckel analysis
also supported this behaviour, where in UIBU demonstrated lower
Py value than IBU. This indicated ease of plastic deformation and
hence better compressibility of UIBU. It may be postulated that the

compaction properties might have altered due to modication of

the solid form of the drug. However, this possibility was ruled out
by performing solid state characterization of UIBU.
Tabletability of the UCIBU was found higher than DCC at all
compaction pressures and an increasing trend was observed with
increasing percentage of coatings. This was attributed to the
improved compressibility of UCIBU over DCC. As discussed earlier, it was an outcome of the formation of percolating network of
UIBU. Signicant improvement in the tabletability was observed
in case of 2.0% UCIBU (P = 0.004). Presence of ultrane particles
on the surface of UCIBU particles, increased the bonding area that
led to better plastic deformation and hence improved tabletability. However, at higher compaction pressure, the compressibility
(and hence tabletability) of DCC and UCIBU was found to be almost
similar. As the particle size of IBU and UCIBU was found almost
similar, the effect of particle size on the compaction properties
was not expected. Compactibility of both the materials was found

Fig. 10. Schematic diagram depicting impact of ultrane coating on ow and compaction behaviour of ibuprofen.

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similar, as coating with the same material did not alter the bonding
strength. Compressibility data was also supported by the Heckel
analysis where in the Py values of UCIBU were found lower than
DCC and a decreasing trend was observed with increasing % of
coating. Py value indicates the pressure required to undergo plastic deformation. Lower Py value of UCIBU indicated ease of plastic
deformation over DCC. As evident from Fig. 9a, 2.0% UCIBU required
around 21 MPa compaction pressure to form tablets of 0.85 MPa
tensile strength. However, DCC required 104 MPa to prepare tablets
of almost similar tensile strength (0.88 MPa).
Thus, up to 2% of coating with ultrane particles can improve the
compressibility and hence tabletability with slight reduction in the
ow properties. However, beyond 2% coating load, the ow properties may worsen. Hence, it is recommended to control the unit
operations so as to control generation of ultrane particles within
2%. Hence, this work has highlighted the pros and cons associated with generation of ultrane particles during the industrial unit
operations. Moreover, this approach can be further explored and
practiced to improve compaction properties of high dose poorly
compressible drugs.
4. Conclusion
Present study reveals the changes in the mechanical behaviour
of the material upon coating of the ultrane particles over the
surface of the core material. This increased bonding area and cohesivity of the material. Flow property of the ultrane coated material
deteriorated slightly. However, the compressibility of the material
improved and led to better tabletability. This study highlighted that
surface coating with the ultrane particles of the same material
signicantly affected bonding area rather than bonding strength
that ultimately governed the compaction behaviour of the material. This work has implications in manufacturing process of tablets
involving micronization and subsequent compaction. This strategy
can also be explored for improving tabletability of high dose poorly
compressible drugs.
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