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International Journal of Pharmaceutics 441 (2013) 527–534
Contents lists available at SciVerse ScienceDirect
International Journal of Pharmaceutics
journal homepage: www.elsevier .com/ locate / i jpharm
Flow and compaction behaviour of ultrafine 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 flow and compaction properties are prerequisites for successful compaction process. Apart from
initial profile, mechanical properties of pharmaceutical powders can get modified 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 hasgreatest implications for formulations like high dose drugs wherein the active pharmaceutical ingredient
(API) contributes the maximum bulk in the final formulation. The present study assesses the impact of
dry coating with ultrafine particles of same material, on the flow and compaction properties of the core
material. Ibuprofen was selected as model drug as it has been reported to have poor mechanical prop-
erties. Ultrafine ibuprofen (average size 1.75m) was generated by Dyno® milling and was dry coated
onto the core ibuprofen particles (average size 180m). Compaction studies were performed using a
fully instrumented rotary tablet press. Compaction data was analyzed for compressibility, tabletability,
compactibility profiles and Heckel plot. Dry coating of the ibuprofen exhibited greater compressibil-
ity and tabletability, at lower compaction pressure. However, at compaction pressure above 220MPa,
compressibility and tabletability of coated as well as uncoated materials were found to be similar. Heckel
analysis also supported the above findings, as P y value of uncoated ibuprofen was found to be 229.49 MPa
and for 2.0% ultrafine coated ibuprofen was found to be 158.53 MPa. Lower P y value of ultrafine coated
ibuprofen indicated ease of plastic deformation. Superior compressibility and deformation behaviour of
ultrafine 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
etal.,2008;Patel et al., 2006). However, poormechanical properties
become a hurdle in successful development of tablet formulation.
This becomes severein case of high dose poorlycompressible drugs
like ibuprofen. Moreover, mechanical properties of pharmaceutical
powders can modify during unit processes like milling. Milling can
generate ultrafine or nano particles that can get coated onto the
bigger core particles and affect the mechanical properties like flow
and compressibility. This may have profound impactin case of high
dose poorly compressible drug. Hence it is imperative to study the
effectof ultrafine coating on themechanical properties of high dose
poorly compressible drug.
Various approaches have beenreportedto improve the mechan-
ical properties of the material. Crystal habit modification 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.: +91172 2214682 2126; fax: +91172 2214692.
E-mail address: [email protected] (A.K. Bansal).
crystallization from different solvents was reported as an aid to
improve the densification behaviour of nitrofurantoin (Marshall
and York, 1991). Bacher et al., showed improved compactibility
and compressibility of calcium carbonate and sorbitol using wet
granulation (Bacheret al., 2008). Theeffect of particle size andcom-
paction force on thecompaction behaviourof paracetamol wasalso
studied (Patel et al., 2007). Co-crystallization of caffeine also led to
improvement in the mechanical properties (Sun and Hou, 2008).
Recently, modification of the surface by coating, has been reported
to improve the flow (Hou and Sun, 2008; Jallo et al., 2011; Yang
et al., 2005) and compaction properties (Shi and Sun, 2011) of a
material.When the materialsblended,differ largely in theirparticle
sizes, the smaller material tend to coat on the coarser material. The
adhering material tends to form a percolating network which gov-
erns 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 flow properties, but deteriorates the com-
paction properties (Sun,2011). For example, dry coating of colloidal
silica (Cab-O-Sil) on the MCC particles improved flow property but
reduced the tabletability (Chattoraj et al., 2011). Improvement in
the flow property was attributed to reduced interaction/bonding
between the particles and ‘ball bearing’ effect. However,
0378-5173/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.ijpharm.2012.10.048
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528 P.K.More et al. / International Journal of Pharmaceutics 441 (2013) 527–534
deterioration of the compaction properties was attributed to reduc-
tion in the bonding strength of the material due to presence of
poorly bonding silica on the surface of MCC.
Ithas also been reportedthat coating of an APIwithhighly bond-
ing 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 ultrafine particles (particles hav-
ing size below 15m) of the same material and its impact on flow
and compaction is still lacking.
Present study assesses impact of coating of ultrafine particles
of same material on the flow and compaction properties of the
core material. Ibuprofen was selected as model drug. Ultrafine par-
ticles of ibuprofen (average size 1.75m) were generated using
Dyno® mill and coated onto core material of average particle size
of 180m, by dry coating method. Compaction behaviour was
assessed using a fully instrumented rotary tablet press and data
was analyzed for compressibility, tabletability, compactibility pro-
file(CTC profile) andHeckel plot. This science based approach helps
to understandthe effectof materialproperties on the processability
of tablets in the perspective of QbD principles (Yu, 2008).
2. Experimental
2.1. Materials
2.1.1. Ibuprofen
Ibuprofen was kindlygiftedby Arbro Pharmaceuticals Ltd., New
Delhi, India. Sample exhibited plate shaped crystal habit. It was
passed through set of sieves and the fraction BSS # 60–80 was used
as ibuprofen core/bulk material (IBU).
2.2. Methods
2.2.1. Generation of ultrafine ibuprofen (UIBU)
Wet milling process was used to generate ultrafine IBU. 10g of
IBU and 100ml of distilled water was introduced into the millingchamber. Twice volume (200 ml) of glass beads of 0.75–1mm 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 ultrafine
suspension was determined using Zeta sizer® (Nano ZS, Malvern,
Worcestershire, UK). Ultrafine suspension obtained by the milling
process was dried overnight at 60◦C in a vacuum oven (Narang Sci-
entific WorksPvt Ltd., NewDelhi, India). The agglomerated material
obtained upon drying was milled using mortar pestle and passed
through BSS # 200 to get loose aggregates of ultrafine IBU (UIBU).
2.2.2. Coating of UIBU on core particles (IBU)
Initially, UIBU and IBU were geometrically mixed. The mix-ture (10 g) was poured into a plastic bottle and 20 g of glass
beads (4–5mm 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, 20min, 30min). The bottle was attached to horizon-
tally mounted shaft of Kalweka® instrument (HD 410 E, Kalweka,
Gujarat, India) and rotated at 150rpm. Different percentages of
ultrafine coatings were applied to obtain ultrafine 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 Bruker’s D8 Advance diffractometer (Bruker
AXS, Karlsruhe, West Germany) with Cu K radiation (1.54 A), at
40kV, 40mA passing through nickel filter. Analysis was performed
in a continuous mode with a step size of 0.01◦ and step time of 1s
over an angular range of 3–40◦ 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 calibratedusing high puritystandardof Indiumfor temperature andheat flow
measurement, respectively. DSC cell was purged with 50ml/min
dry nitrogen. Accuratelyweighed samples (1–2mg) were heatedin
standard aluminium pans in the temperature range of 25 to 100◦C,
using a heating rate of 10◦C/min.Low temperature DSCof 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). Sam-
ples 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 Microsys-
tems, 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 accu-
rate moisture determination. Sample size of approximately
200mg was utilized for the moisture content determina-tion.
Scanning electron microscopy (SEM) of UIBU, DCC and 2.0%
UCIBU was performed using a scanning electron microscope (S-
3400, Hitachi Ltd., Tokyo, Japan) operated at an excitation voltage
of 10kV at different magnifications. 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 flow properties
True density (n= 3) of IBU was determined by helium pycnome-
ter/true density metre (Pycno 30, Smart Instruments, Mumbai,
India). Bulk density (n=3) of DCC and UCIBU samples was deter-
mined using a 100ml measuring cylinder. Bulk density of UIBU
(n=3) was determined using a 10ml measuring cylinder. Tapped
density (n= 3) ofthe samples wasdetermined bybulk density appa-
ratus (ETD 1020, Electrolab, Mumbai, India) using USP method I.
Flow properties of the materials were determined by calculating
Hausner ratio and Carr’s 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 400mg ofmaterials upto 35MPa compaction pressure
in a hydraulic press with a dwell time of 2 s using 13mm punch die
set. The tablets were further characterized for weight, thickness
and hardness.
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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 flat punch tip. Feed frame was used for
uniform die filling 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±5mg. The applied compaction force
was controlled by the pressure roller with a hand wheel. Com-
paction force was initially adjusted to low and increased gradually
to collect data at different compaction pressure. Tableting was per-
formed at the constant speed of 14rpm. 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 wascalculated 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
thetablet.The solid fraction of thetablet wascalculated 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 profile 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 poros-
ity 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 transforma-
tion of the parametric force and displacement relationship (Patel
et al., 2010). Itis represented by the Plot of ln [1/1−D] against com-
paction 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 pres-
sure (P y) (Heckel, 1961).
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 IBUduring thewet
milling process. Average particle size of the ultrafine suspension
was found tobe 1063nm (PDI0.469) byZetasizer®. No stabilizer(s)
was included as it may have altered the compaction properties
of IBU. Drying of ultrafine suspension produced aggregates which
were milled using mortar pestle and passed through BSS # 200.
This gave a powder of mean diameter of 1.75m and a range of
0.5–3.1m.
Fig. 1. Plot of particle size distribution of IBU against glass beads/IBU ratio for
processingtimeof (a) 10min, (b) 20minand (c) 30min.
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 signifi-
cantly 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 20min processing time were selected (Fig. 1b). Three different
dry coated batches 0.5% UCIBU, 1.0% UCIBU and 2.0% UCIBU, con-
taining 0.5,1 and2.0% of UIBUcoating,respectively,were generated
using this optimized method.
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 180 168 175 178
D90 230 214 212 216
Moisture content (%) 0.063 (0.005) 0.08 (0.010) 0.09 (0.017) 0.076 (0.005)
Standard deviations are given in parentheses.
3.3. Solid state characterization
Particlesize distribution and moisturecontentof DCC andUCIBU
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).
PXRDpatternforIBU,UIBUand2.0%UCIBU(Fig.2) showedsharp
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
intensityof the peaks decreased probably dueto 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 melt-ing 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 127.9J/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 amor-
phization 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 indicat-
ing 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 inthe 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 129.3J/g.
Thermal events of IBU, UIBU and 2.0% UCIBU were also visual-
ized using HSM and they corroborated findings of DSC. However,
HSM of 2.0% UCIBU revealed interesting information. As shown in
Fig. 5, ultrafine particles showed melting at 73.3 ◦C (Fig. 5c and d),
Fig. 3. DSCoverlay of IBU, UIBU and 2.0% UCIBU.
followed by melting of the core IBU particles at 78.5◦C (Fig. 5e andf). This further confirmed 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 dif-
ferent magnifications. DCC crystals exhibited irregular plate shape
habit (Fig. 6a). Surface of the DCC particles was found rough at
the magnification 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 ultrafine particles on the surface (Fig. 6d and
f). SEM images of UIBU showed particles in the ultrafine range
(0.5–5m) (Fig. 6g and h). Particle size of the ultrafine particles
present on the surface of the IBU particles also determined using
SEM (n= 25). Particle size was found in the range of 0.4–2.4m.
3.4. True density and flow 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 significantly lower bulk density, as compared to DCC. A
similar trend was also seen in case of tapped density. Carr’s index
and Hausner ratio were evaluated as marker of flow properties.
UIBU showed significant increase, whereas 0.5, 1.0, 2.0% UCIBU
showed marginal increase in that order (Table 2). Poor flow prop-
erty 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 flow 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 char-
acterization of the tablets. Tabletability of UIBU wasfound superior
over IBU at all compaction pressures as shown in Fig. 7.
Fig. 4. DSCthermogram of UIBU at lowtemperature (−60 to 2 5◦
C).
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Fig. 5. HSM of 2.0%UCIBU(a) 32.1◦C normalmode, (b)33.1◦C polarized mode, (c)73.3 ◦C normal mode, (d)74.0◦C polarized mode, (e)78.5◦C normalmodeand (f) 78.8◦C
polarized mode.
Compressibility of UIBU was also found greater than IBU at all
compaction pressure (Fig. 8). Compactibility profile of both the
materials was found similar. P y values of IBU and UIBU were found
to be 50.54 MPa and 18.98 MPa, respectively.
3.5.2. Instrumented rotary tablet press
CTCanalysisof DCC, 0.5% UCIBU,1.0%UCIBU and2.0%UCIBU was
carried out using the compaction data obtained by instrumentedrotary tablet press. Tabletability is the ability of the material to
be transformed into tablets of sufficient strength upon applica-
tion of compaction pressure ( Joiris et al., 1998). Increasing trend in
the tabletability was obtained upon increasing coating with ultra-
fine particles of IBU (Fig. 9a). Tabletability of DCC and 2.0% UCIBU
was significantly 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 com-
paction 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 sufficient tensile
strength under the effect of densification ( Joiris et al., 1998). Com-pactibility of DCC and UCIBU were found similar at all compaction
pressure (Fig. 9c). Heckel analysis was also performed using the
compaction data (Fig. 9d). P y value for DCC, 0.5%, 1.0%, and 2.0%
UCIBU was found to be 229.49, 194.12, 168.00 and 158.53MPa.
UCIBU showed significantly lower P y v alue than DCC and fur-
ther a decreasing trend was observed with higher percentage of
coating.
3.6. Impact on flow behaviour
Present work demonstrated significant impact of ultrafine coat-
ing i.e. coating with ultrafine particles (average size 1.75m), onthe coarser particles (average size 180m) of the same material
on the mechanical properties of IBU including its flow behaviour.
Flow properties of the coated materials were found different than
control material. Ultrafine particles tend to coat on the surface of
bulk particles, as they possess high surface energy (as evident from
the SEM images). Ultrafine particles present on the surface formed
a percolating network that enhanced interactions between the par-
ticles. This led to increase in the cohesivity of the material (Fig. 10).
Increased Carr’s index and Hausner ratio of UCIBU over IBU indi-
cated deterioration of the flow properties that was attributed to
increase in the cohesivity of the material. Moreover, an increas-
ing trend was observed (in both the cases) upon increasing coating
load. This indicated worsening of flow properties upon increasing
coating load, due to formation of a more cohesive and strong per-colating network. Cohesive materials tend to form aggregates and
demonstrate poorflow. Such materialsare difficultto packthan free
flowing materials (Luo et al., 2008). This explains the decreasing
trend of bulk and tapped density of UCIBU, upon increasing % of
Table 2
Bulk and flow properties of materials.
Material Bulk density Tapped density Carr’s index Hausner ratio
DCC 0.534 (0.003) 0.682 (0.005) 21.621 (0.136) 1.275 (0.008)
UIBU 0.308 (0.002) 0.495 (0.004) 37.823 (0.181) 1.608 (0.005)
0.5% UCIBU 0.509 (0.007) 0.678 (0.005) 24.989 (1.120) 1.333 (0.020)
1.0% UCIBU 0.491 (0.005) 0.678 (0.003) 27.500 (0.562) 1.379 (0.006)
2.0% UCIBU 0.467 (0.003) 0.662 (0.013) 29.365 (1.375) 1.416 (0.028)
Standard deviations are given in parentheses.
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Fig. 6. SEM images (a) DCC 300× magnification, (b) 2.0% UCIBU 300× magnification, (c) DCC 1000× magnification, (d) 2.0% UCIBU 1000× magnification, (e) DCC 10,000×
magnification, (f) 2.0% UCIBU 10,000× magnification, (g) UIBU 6000× magnification and (h) UIBU 15,000× magnification.
Fig. 7. Tabletability of IBU and UIBU. Fig. 8. Compressibility of IBU and UIBU.
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Fig. 9. Compaction data analysis of DCC, 0.5% UCIBU, 1.0% UCIBUand 2.0% UCIBU (a)tabletability plot, (b) compressibility plot, (c) compactibility plot and (d)heckel plot.
coating. Hence, dry coating with ultrafine particles, slightly deteri-
orated the flow 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). Modification 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. Ultrafine par-
ticles enhanced the overall bonding area thus facilitating plastic
deformation and compressibility. Findings from Heckel analysis
also supported this behaviour, where in UIBU demonstrated lower
P y 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 modification 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 ear-
lier, it was an outcome of the formation of percolating network of
UIBU. Significant improvement in the tabletability was observed
in case of 2.0% UCIBU (P = 0.004). Presence of ultrafine particles
on the surface of UCIBU particles, increased the bonding area thatled to better plastic deformation and hence improved tabletabil-
ity. 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 ultrafine coating on flow and compaction behaviour of ibuprofen.
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