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Pradnya Patil et al.

IRJP 2012, 3 (1)

INTERNATIONAL RESEARCH JOURNAL OF PHARMACY


www.irjponline.com ISSN 2230 8407
Research Article
APPLICATION OF SPHERICAL AGGLOMERATION TECHNIQUE TO
IMPROVE
MICROMERITIC PROPERTIES AND DISSOLUTION
CHARACTERISTICS
OF NABUMETONE
2
,2
Pradnya Patil1 *, V R M Gupta 2 , R.H Udupi1 , B Sree Gir i Prasad2 , Nikunja
, K Sr
Patiikanth
N Devanna3 , M Rama Devi2
N.E.T Pharmacy College, Raichur, Karnataka, India
Pulla Reddy Institute of Pharmacy, Annaram (V), Hyderabad, Andhra Pradesh, India
3
H.O.D, Department of Chemistry, JNTU, Ananatapur, Andhra Pradesh, India
1

Article Received on: 01/11/11 Revised on: 2 1/12/11 Approved for publication: 09 /01/12

*E-mail: pradnyapatil_4u @yahoo.co.in


ABSTRACT
T he present work is aimed to enhance the solu bility and dissolution rate of Nabumetone,
4-(6-methoxy -2-naphaleny
water
l)-2-butano
insoluble
ne an tiinflammatory dru g by spherical agg lomeration technique usin g a solvent change method consisting o f acetone, water and
dichloromethane
as solvent,
solvent
an d bridging
liquid non
respectively. The hydrophilic poly mers like poly vin yl pyrrolidone K-30 (PVP) and sodium alginate were
used
in the pro cess. In frared (I.R) spectroscopic studies, Differential scanning calorimetery (DSC) and Scanning electron microscopy
agglomeration
(SEM)
were u sed
characterizatio
n offorpure dru g and its agglomerates. The I.R spectroscop y revealed that there is no chemical interaction between drug
and
polymers,
indicated that noalso
chemical changes in the crystallized agglomerates .The agglomerates exhibited significantly improved solubility,
dissolution
and
micromeriticrate
properties
(angle o f repose, Carr s index,
bu lk density, tap ped density. Hausner
compared
s ratio)
with pure drug Nabu meton e. The aqueous
solubility and dissolutio n rate of the drug from spherical agglomerates was significan tly ( < 0.05) increased
p (nearly two times). SEM stu dies revealed that the
agglomerates possess a go od spherical shape. The stud y revealed that Micromeritic Properties, Solu bility and Invitro drug release rate
is
increased
withconcentration from 0.25 % to 1% as compared to sodium alginate.
increase
in PVP
Keywords : Nabumeton e, agglomeration technique, solubility, dissolution rate, micromeritic properties.
9
INTRODUCTION
.The
spherical
technique
formhad
been used to improve the
Much research has been conducted in to methods of
powder micromeritic properties (flowability and
10, 11, 12
improving drug solubility and dissolution rates to increase the
compressibility) and dissolution of . drug
Then
1
oral bioavailability of hydrophobic drugs . Consequently,
polymers were introduced in this system to modify their
14
many hydrophobic drugs show erratic and incomplete . The various
release13,parameters
were optimized in this
absorption from the gastrointestinal tract of animals
such asand
type, amount and mode of addition of bridging liquid,
humans, which may lead to therapeutic failure.temperature,
Thus, one ofagitation speed and reaction time to get more
the major challenges to drug development today
practical
is pooryield of spherical agglomerates. General methods of
solubility, as an estimated 40% of all newly developed drugs
spherical crystallization are spherical agglomeration,
2-5
are poorly soluble or insoluble in water
. Also
emulsion
formulation
solvent diffusion and ammonia diffusion method.
and manufacture of solid oral dosage forms andThe
tablets
principle
in
steps involved in the process of spherical
particular have undergone rapid changes and crystallization
development are flocculation zone, zero growth zone, fast
15
.
over the last several decades. The basic requirement for
growth zone and constant
Nabumetone
size zoneis widely
commercial production of tablet is a particulate
used
solid
in the
withtreatment of inflammation and pain associated
6
.
good flowability, mechanical strength and compressibility
with rheumatic
disorders such as rheumatoid arthritis,
Now a day s pharmaceutical industry prefers direct
osteoarthritis and also postoperative pains. It exhibits poor
compression technique because of its economical
flowfacility
and compression
in
characteristics and is hence a suitable
processing without the need of moisture and heat
candidate
with less
for spherical crystallization process to improve the
16
number of processing steps. In direct tabletting method, it is
flow properties and. compressibility
To reach the valuable
Page
156
necessary
bulk
mixture
strength
efficiency
increase
solubility
methods,
enables
agglomeration
developed
spherical
by
carried
directly
which
powder
out
the
to
to
of
bioavailability
crystallization
spherical
of
to
both
control
by
fine
the
simultaneously
the
the
increase
inKawashima
is
tabletting
compacted
crystals
crystallization
manufacturing
order
abulk
the
size
crystallization
type
flowability
drug
to
enlargement
produced
of
as
machine
retain
and
in
tablets
the
ainpowder
novel
1986
size
process
one
and
drug
ain7and
is
of
.steady
step
agglomeration
technique
the
In
and
agglomeration
by
athe
addition
sufficient
.compressibility
crystallization
versatile
is
improving
that
Among
he
crystals.
supply
also
has
can
which
important
involving
to
goal
simple
aSpherical
defined
Nabumetone
process
the
mechanical
on
Spherical
NSAID
transform
of
bridging
shall
increasing
technique
the
purchased
isof
Hyderabad,
basis
various
powder
into
first
of
improving
agglomeration
be
to
that
agood
the
agglomerates
drug
liquid
ofchemicals
miscibility
was
from
solvent
Nabumetone
India.
(dichloromethane).
aqueous
EXPERIMENTAL
Materials
Process
the
a S.D.
therapeutic
gift
technique
used
(acetone),
of
PVP
development
of
solubility
sample
Fine
Nabumetone
were
solvent
K-30
it Chemicals,
is
using
efficacy
of
afrom
essential
poor
of
&Sodium
analytical
Here
and
drug.
awere
and
three
Devis
solvent
agglomerates
of
solubility
India.
optimization
to
prepared
water
solvent
reagent
alginate
Laboratories,
improve
(water)
All
insoluble
ofsystem
by
grade.
other
were
drug
and
the
8it

Pradnya Patil et al. IRJP 2012, 3 (1)

formulated using dichloromethane as bridging liquid


method
whichof crystallization was optimized and validated
helps in binding of agglomerates by wetting the surface of
according to the study of variables.
agglomerates. The spherical agglomerates were formed by
Method of preparation of agglomerates
aggregation of these dispersed crystals. In this study In
wethis
usedstudy, solvent change method was used for the
the hydrophilic polymers like sodium alginatepreparation
and PVP toof spherical crystals of Nabumetone. The drug
provide strength and sphericity to the agglomerates. It was
Nabumetone (2gm) was dissolved
(a goodinacetone
solvent)
observed that PVP is more hydrophilic as compared
hydrophilic
to
polymers
and
(PVP K-30 and Sodium alginate,
sodium alginate in improving micromeritic properties which
0.25 1%, m/V) in 100 ml
Thedistilled
drug solution
water.
ultimately increase the water solubility as wellwas
as in
added
vitroto a polymeric solution which was maintained
release.
with continuous stirring at speed of 500 25 RPM. The
Designing the spherical crystallization processbridging
requiresliquid dichloromethane was added drop wise with
optimization of various process variables, which could
mechanical
affect stirring for 30 minutes. The spherical crystals
the preparation and properties of the spherical crystals.
were collected
The by filtration and dried at room temperature for
.
2hours
Table - 1: Effect of variables on formulation of spherical agglomerates o f Nabumetone

17

S.NO PARAMETERS VARIABLES OBSERVATION


1 Bridgin g liquids Hexane No agglomerates
Toluene lump formation
Dichloromethane Sp herical agglomerates
Benzen e No formation of agglomerates
Chloroform lump formation
2 Amount of bridging liquid (ml) < 2.8 No agglomeration
2 .8 Sp herical agglomerates
> 2.8 Irregular shaped agglomerates
3 Agitation speed(rpm)

3 00No agglomeration
4 00 Sp herical but large agglomerates
5 00 Sp herical agglomerates
6 00 Irregular but small shaped agglomerates
7 00 Irregular but small shaped agglomerates

4 Agitation time (min) 5 No Spherical agglomerates


15 In complete agglomerates
30 Sp herical agglomerates

CHARACTERIZATION
volumetric flask filled with water and 2% SLS. The
IR, DSC & SEM Studies
volumetric flasks were shaken for 2 h on mechanical shaker.
The infrared (IR) spectra of powder Nabumetone,
The solution
physicalwas filtered through Whatmann filter paper No.
mixture and the agglomerates were recorded on an IR- 1 and the drug concentration was determined
spectrophotometer (FTIR 8300, Shimadzu, Japan) by
spectrophotometrically
the KBr
at 271 nm. Each sample was done in
pellet technique. Differential scanning calorimetry (DSC)
triplicate.
analysis was performed using a DSC-60 calorimeter
In vitro Dissolution Studies
(Shimadzu).The surface morphology of the agglomerates was dissolution
The in vitro
studies were carried out using 8
assessed by scanning electron microscopy (SEM)
stations
(Leica
USP 23 dissolution testing apparatus (Electro lab,
StereoScan 430, LEO, UK).
India). The dissolution medium used was 900 ml of 2%,
m/
v
Micromeritic Properties
sodiumlaurylsulphate (SLS). The agglomerates containing
The loose bulk density (LBD) and tapped bulk density
500 mg
(TBD)
of Nabumetone were weighed and filled into a hard
of pure drug Nabumetone and its spherical crystals
gelatin were
capsule. In the case of pure drug, 500 mg of pure
determined using measuring cylinder method. Carr
Nabumetone
s index was weighed and filled into a capsule. The
was calculated using LBD and TBD values 18 .The
capsule
angle
wasofthen introduced into the dissolution medium. The
19
repose
amount
funnel
diameter
calculate
Drug
dissolving
followed
diluted
1700,
Solubility
The
and
spherical
solubility
2%
drug
Loading
UV-Visible
fixed
was
solution
of
SLS
the
agglomerates
(2
by
Studies
loading
100
agglomerates
assessed
r)
angle
measuring
atof
was
Efficiency
of
mg
anabumetone
spectrophotometrically
Shimadzu)
of
the
constant
efficiency
determined
of
by
repose
and
pile
crystals
the
the
was
adding
fixed
of
height
as
at
absorbance
spherical
oftan
allowed
powder
271
by
infunnel
crystals
to100
taking
nm.
(=screw-capped
agglomerates
h).The
were
h/r.
method
to
ml
(PharmaSpec
of
was
excess
flow
of
appropriately
measured
height
determined
methanol,
agglomerates
through
studied
medium
quantity
50
The
. in
Nabumetone
A(h)
ml
the
water
UVknown
to
interaction
by
drug
aof
and
was
Graph
by
of
IR
The
are
Nabumetone,
spectroscopy
stirred
The
results
shown
Pad
spectrophotometrically.
Statistical
mean
software.
RESULTS
IR
showed
between
Studies
samples
Instat
atwere
dissolution
75
incharacteristics
Fig
Software
rpm
)analysis
the
and
physical
analyzed
AND
was
were
1using
drug
DSC.
calculated
and
time
DISCUSSION
collect
(GPIS;
by
mixture
and
aThe
Table1.
(paddle
two
MDT
peaks
IR
the
edusing
tailed
Version:
IR
peaks
and
polymer
at
atPage
spectra
37
-test
the
3062
Student
spherical
analyzed
of0.5
Origin
using
1.13)
.157
pure
was
The
cm
C.
of
st20

Pradnya Patil et al. IRJP 2012, 3 (1)

(aromatic C-H stretching),2956&2848 cm -1 , 2916 & 2812


Scanning Electron Microscopy Studies
cm-1 (C-H stretching of CH
-O-CH
and
CH
Physical
groups
characterization
of agglomerates can be done by
3
3
2
-1
asymmetric and symmetric resp.) ,1705 cm SEM analysis t o assess typical shape of agglomerates and
-1 (C=C untreated
(C=O),1634,1608,1505&1485 cm
ring
drug. The spherical single agglomerate is formed
-1
-1
stretching),1452&1387cm , 1410&1363cm (C-H
by closel
bending
y compacted fine rectangular shaped crystals which
of CH3 ,OCH3 ,&CH2 groups asymmetric and symmetric)
give ,evidence of enlargement of crystal surface of
1028cm -1 (C-O-C) ,957,895,845cm - 1 (fused andNabumetone
substituted leading to increase flowability and compression
aryl rings).The comparison of IR spectra of pure
property.
drug,The surface morphology of prepared agglomerates
physical mixture of drug and polymer along with
with 1%
that PVP
of and polymer is shown in figure 4. (36X) and
spherical agglomerates of Nabumetone (NA-P-4) figure
reveals
4 that
(160X) of D, E, F. and also spherical agglomerates
there is no change in position of characteristic ofabsorption
Nabumetone shown figure 4 figure 4 (100X, B) were
bands. This suggests that the drug has not undergone
spherical but no sphericity and smooth surface. The SEM
interaction with pol ymer (sodium alginate, PVP K analysis
30) and showed that the prepared agglomerates were
other excipients.
spherical in shape with smooth and regular surface.
DSC Studies
Micromeritic Properties
DSC thermograms were shown in Fig 2 for pure
The drug
results of loose bulk density (LBD) and tapped bulk
Nabumetone and polymers PVP K30 & Sodium
density
Alginate.
(TBD) are presented in Table - 2. These parameters
The DSC study indicates that there is no appreciable
were
change
used to assess the packability of the crystals. The pure
in the nature of thermo grams. The pure drug showed
drug powder
sharpwas more bulky and fluffy, which was indicated
endothermic peak with highest peak area at a melting
by the
point
lowest
of LBD value (0.184 0.00058 gmL-1,n=3).The
81.130 c, which is in agreement with the literature
highest
M.P. TBD
The value (0.278 0.001gmL-1,n=3)of pure drug
DSC thermogram of the formulation of spherical agglomerate
indicates a high intergranular space between particles. In
of Nabumetone with PVP K30 and sodium alginate
contrast,
showed
the spherical agglomerates exhibited higher LBD
endothermic peaks with comparatively reduced areas
(0.231
at 0.0015 to 0.253 0.0005 gmL-1,n=3) and TBD
melting point of 79.820 c and 79.680 c. The lowering
(0.247 of0.00057
m.p
to 0.277 0.00058gmL-1,n=3)values. These
shows that change may be due t o crystallization of
results
drug with
indicate good packability of the prepared spherical
solvent acetone. As there is no much change in the thermalcrystals when compared with pure Nabumetone.
behavior of the drug and its formulations as indicated
The by
results
the of Carr s index, Hausner s ratio and angle of
thermo grams, it can be concluded that the drug hasrepose
retained
of spherical crystals in comparison with pure drug are
its identity even in formulations and indicates there
presented
is noin Table - 2. These parameters were used to assess
interaction between the drug and polymers used in
thetheflow
present
and compressibility properties of the agglomerates.
study.
Carr s index and Hausner s ratio of pure drug were
XRD Studies
33.57 0.0058% and 1.50 0.0058(n =3),respectivel y,
X-ray powder diffractometry (XRPD) is a powerfulindicating
techniqueextremely poor flow properties. The powder could
for the identification of crystalline solid phases. not
Every
pass through the funnel during the angle of repose
crystalline solid phase has a unique XRPD pattern,
experiment.
which canThe poor flow of Nabumetone could be due to
form the basis for its identification. The X-ray
the powder
irregular shape and high fineness of the powder, which
diffraction pattern in the range 2 -50 showed inposed
Fig 3, hurdles
that
in the uniform flow from the funnel. On the
the characteristic diffraction peaks of Nabumetone
otherwhich
hand, all the prepared spherical agglomerates exhibited
were still detectable in the crystallized samples,low
suggesting
Carr s index, Hausner s ratio and angle of repose values,
that the particles get crystallized in the presence indicating
of sodium excellent flow properties and compressibility
alginate and PVP-k-30 did not undergo any structural
(Carr s index: 5.70 0.0153 to 9.88 0.005%,n=3: Hausner s
modifications. However, the differences in the relative
ratio:1.07 0.01 to 1.11 0.005,n=3;angle of repose:23.02
intensities of their peaks are due to the differences in0.27
the to 27.09 0.0058o,n=3). Similarly the spherical
crystallinity of particle size of the samples andagglomerates
decrease in of Nabumetone prepared without polymer (SP)
the intensities may be due to change in sphericity.exhibited
It is very
low Carr s index, Hausner s ratio and angle of
difficult to identify the presence of sodium alginate orrepose
PVP- values, indicating excellent flow properties and
k-30 in XRPD spectra as they are pol ymers withcompressibility
amorphous
(carr s index:10.5 0.0058%,n=3; Hausner s
structure and therefore no Sharp peaks are apparent
ratio:1.11
at
0.0058,n=3;angle of repose:28.49 0.015o,n=3).
particular
2
due
to
the
very
low
crystallinity
The
of
the
improved
of
spherical
158
components in the form of spherical agglomerates.agglomerates may
. flowability
Among
size
the
good
be agglomerates
due
ofmicromeritic
all
crystals
toand
the
the compressibility
sphericity,
prepared
prepared
properties
spherical
regular
, with
PVP
. Page
and
1%,
exhibited
crystals,
larger
m/
V
)

Pradnya Patil et al. IRJP 2012, 3 (1)


a

Table 2: Micromeritic properties of agglomerates and pure drug


Spherical
crystals

LBD
(g mL 1)

TBD
(g mL 1)
b

0.276 0.18

Carr s index
(%)
b

Angle
Particle
of
Size
repose ( ) ( m)
b

0.253 0.001

NS2

0.237 0 .0 015

0.263

0.00058

9.88

0.01 b

1.11 0.005

NS3

0.253 0.0005

0.277

0.00058

8.66

0.02 b

1.09 0.005

26.56 0 .0 099 239 .8 8 0.10

NS4

0.237 0.0005

1.11 0.005

26.86 0.005 251 .1 8 0.12

1.07 0.005

24.75 0.01 208 .1 2 0.13


229 .0 8 0.15b

NP1

0.241 0 .0 005

NP2

0.231 0.0015

NP3

0.231 0.001

NP4

0.248 0.00152

DRUG

0.184 0.00058

SP

0.247 0.00057

0.001 b 9.88

0.258

0.00153

0.247

0.0005

0.247

0.00057

0.263

0.001

b
b
b

0.0058
6.48 0.01

6.48

0.005

6.59

0.0153

1.07 0.01

b
b

1.5 0.0058
1.11 0.0058

0.12

257 .0 3 0.11b
23.62 0.02
b

1.07 0.0152

10.5 0.0058

b 24.57

0.01

0 .2 78 0.001 33.57 0 .0 058


0.276 0.00058

b 1.07

0.01528

5.70

1.09 0.01

25.641990.13
.5 2 0.12b
218 .7 7 0.11b
b
27.09 0 .0 058

NS1

0.263

8.33 0.01

Hausner s
ratio

23.02 0.27 263 .0 2 0.10


87.09 0.12b
-----

28.49 0.015 131 .8 2 0.22

LBD loose bulk den sity, TBD tapped bulk density.


a Mean SEM,
n = 3.
b Significantly different compared to pure Nabumetone (

p < 0 .0 5).

Drug loading and solubility studies


The results of drug loading efficiency and aqueous solubility are shown in Table - 3.
The drug loading
efficiency
of spherical
agglomerates
is in
the range
93.7 2.3 =to3),
98.6
indicating
1.3 ( negligible
n
loss of drug during the crystallization
process. The results of solubility studies indicate that pure Nabumetone possesses a
very1low
1.1 g (438 1.3
, n =solubility
, nits surfactant property. Solubility of spherical
mL
3) while in
aswater
in 2%(2.43
SLS shows
= 3)g mL
because1 of
1
agglomerates without polymer showed (3.1 1.2 g mL
= ,3)nwhere as in 2% SLS showed (582.2 1.1 g=mL
3).
n,1
However the drug solubility from the Spherical Agglomerates increased < 0.05), demonstrating
p
that the
incorporation
significantly (of Sodium Alginate and PVP K30 as polymers in different
1
1
concentrations
the(5.37
drug solubility
water
, n = 3) to (7.64 1.1; 831.1 1.2
,n
as
well as in 2%enhances
SLS from
1.2; 617.8in 1.1
g mL
= 3)gby
mL
improving
wettability. Maximum solubility from spherical agglomerates was observed at 1%
n=,1
(m/V)
PVP-K30
1.1 g mLwith 2% (m/V) SLS (Table - 3).
3).
Similar
results(7.64
were observed
a

Table - 3: Drug lo ading efficiency and Solubility data for the Agg lomerates and Pure drug
Spherical crystals

Drug loading (% )

So lubility ( g mL

Water
( gm/ml)
NS1
NS2
NS3
NS4
NP1
NP2
NP3

98.2

1.2

96.0

1.3

94.6

1.3

94.2

1.2

98.7

1.3

97.3

1.1

95.5

1.2

SLS
(2%m/
V),

5.37 1 .2

617.8 1.1c

5.42 1 .0

631.1 1.5c

5.73 1 .4

648.9 1.3c

5.82 1 .5

657.8 1.1c

7.33 1 .8

804.4 1.5c

7.46 1 .6

813.3 0.5c

7.51 1 .3

823.2 1.3c

93.7 2.3
cPage
159
.Dissolution
,with
In with
The
and
the
MDT
Spherical
3)
Vitro
Table
end
results
14.47
MDT
of
Evaluation
5.
agglomerates
of
180
Pure
(13.68
0.30
in min
vitro
drug
min,
0.30
in
Nabumetone
dissolution
n=3
in
2%
min,
2%SLS
SLS
n=3).studies
69.88
(was
Spherical
(loading
rate
are
71.581
0.2%,
less
shown
of
1.0%
Nabumetone
showed
dissolution
release
nsodium
2%
0.2%,
in
=PVP
min,
SLS
at
increased
was
nalginate
5mg
time
n=3)
(11.10
low
(MDT)
0.2,
to
dissolution
and
(13.16
of(min,
compared
spherical
concentration
to(96.44
0.30
=
rate
n=3).
3)in
with
agglomerates
to
This
that
0.2
n=3);
SLS
MDT
incould
of
range
but
pure
(14.22
increase
containing
of
be
thedrug
(76.966
due
mean
0.30
in
tocc
DRUG
NP4
SP
bexhibited
Drug
c Significantly
isagglomerates
expressed
different
compared
asFig.
a3)
%
Mean
orwith
93.3
100
to=
SEM,
of
pure
drug
0.0
1.3
2.43
3.1
Nabumetone
1.2
per
1nwhen
.10.30
100
= n=3)
3.PVP
mg
of
cry
stals.
pmin,
<2%
0.05).
7.64
1n.1
438.2
1.1
1.3
831.1
1.2
c 582.2

Pradnya Patil et al. IRJP 2012, 3 (1)


increased wettability of the drug by the presence of PVP.Kamble R,4)Maheshwari M, Paradkar AR and Kadam S .Melt solidification
technique:
This might be due to the surfactant property of SLS on
the Incorporation of higher wax content in ibu profen beads. AAPS
PharmSciTech. 2004; 5(4): Article 6.
drug which shows maximum dissolution of drug within 5)120
Kapsi SG , Ayres JW. Processing factors in development of solid solution
min. The mechanism behind the solubility and dissolutionformulation of itraconazole for enhancement of drug dissolution and
bioavailability. Int. J. Pharm. 2001; 229:19 3-203.
rate enhancing effect of Nabumetone in crystal form may
, Srivastava, Monika Sharma, Vinita
6) M.M.Gupta B.
pherical
Arya.
S
resemble the solid dispersion mechanism despite the large
a tool of particle engineering for making drug powder
particle size of the crystals. This effect may be due t suitable
o crystallization:
for direct compression. International Journal of Pharma Research
improved wettability of the surface of crystals by the
and Development.2010; 12(1):1-10.
adsorption of PVP onto the surfaces of crystals 21 . They also 7) Shangraw, R.F, Compressed Tablets by Direct Compression. In
demonstrate that PVP is a suitable polymer for the pharmaceutical Dosag e Form: Tablets, Lieberman, H. A., L. Lachman and
J.B. Schwartz (Eds). Marcel Dekker, New York Vol. 1, 1989; 195-246.
preparation of spherical agglomerates of Nabumetone. 8) Gharaei-Fathabad,
E., Biosurfactants in pharmaceutical industry: A minia

Table 4 . Drug release and MDT

Spherical
Agglomerates
NS1

SLS (2%,
Nabumetone Released
(% )
1 00.0 0.0 (after 3h)

MDT (min)
b
b

1 00.0 0.0 (after 3h)


1 00.0 0.0 (after 3h)

15.81 0.11
14.22 0.35

NS4

1 00.0 0.0 (after 3h)

13.13 0.10

NP1
NP2

1 00.0 0.0 (after 3h)


1 00.0 0.0 (after 3h)

13.91 0.11
13.44 0.30

NP3

1 00.0 0.0 (after 3h)

13.16 0.31

NP4

1 00.0 0.0 (after 2h)


1 00.0 0.0 (after 3h)

11.10 0.16
14.47 0.29

1 00.0 0.0 (after 3h)

13.68 0.11

MDT mean dissolution time.


a Mean SEM,
n = 3.
b Significantly different compared to pure Nabumetone (

10) Kawashima, Y. Development of spherical crystallization tech nique and


its application to pharmaceutical system. Arch. Pharm. Res 1984; 7: 145151.
b
11) Kawashima Y, Cui F, Takeuchi H, Niwa T, Hin o T, Kiuchi K.
b

16.58 0.21

NS2
NS3

DRUG
SP

review. AM. J. Drug Discovery Dev 2011; 1: 5 8-69.


9) Kawashima Y., Ok umura M. and Takenaka
SphericalH.
cry stallization:
direct spherical agglomeration of salicylic acid crystals during
crystallization . Science, 1982; 216: 1127-1128.

m /V)

bImprovements

in flowability and compressibility of pharmaceutical cry stals


for
direct
tabletting
by spherical crystallization with a two solvent system,
b
Powder Technology 199 4; 78: 151-157.
b
12) Bodmeier R, Paeratakul R. Sph erical agglomerates of water-insoluble
b
drugs, J Pharm Sci 1 989; 78: 964-967.
b

13) Di Martino P, Barthelemy C, Piva F, Joiris E, Palmieri GF, Martelli S.


Improved dissolution behav ior of fenbufen by spherical crystallization, Drug
Dev Ind Pharm 1 999; 25: 1073-1081.
14) Sano A, Kuriki T, Kawashima Y, Takeuchi H, Hino T, Niwa T. Particle
p < 0.05 ).
design of tolbutamide by spherical crystallization tech nique. IV,
Improvement of dissolution and bioavailability of direct compression tablets
b

prepared using tolbutamide agglomerated cry stals,Chem .Pharm.Bull 1 992;


CONCLUSION
40: 3030-3035.
The present study shows that spherical agglomerates of
15) Yadav A.V, Designing of pharmaceuticals to improve physicochemical
Nabumetone prepared with PVP exhibited improved
properties by spherical crystallizatio n technique, Jou rnal of Pharmacy
micromeritic properties which are essential requirement for
Research. Oct-December 2008; 1(2): 105-1 12.
16) Kulkarni P.K; Subash Chandra Bose .P, Spherical Agglomerates of
direct tableting. Hence in addition to improving the solubility
Nabumetone, Indian Journal of Pharmceutical Education and Research Janenhanced dissolution rate was observed compared to pure
mar 2007; 41 (1):18.
drug Nabumetone. So this technique may be applied for17) Chorasia M. K. Preparation and characterisation of agglomerated
producing oral solid dosage forms of Nabumetone with
spherical crystals of ibuprofen. Indian Journal of Pharmaceutical Science,
2007; 364-368.
improved dissolution rate and oral bioavailability.

18) J. Wells, Pharmaceutical preformulation, the physicochemical properties


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Page 160

Pradnya Patil et al. IRJP 2012, 3 (1)

Fig 1: Photographs showing effect of process variables on Ag glomeratio n (A) Lump formatio n (B) Spherical agglo
(C) Irregular shaped
merates
agglomerates (D) Spherical ag glomerates (E)Spherical but large agglomerates (F) In co mplete agglomerates

Fig 2: IR Spectra of (A) Pure drug Nabumetone; (B) Spherical agglomerate of Nabumetone; (C) Nabumetone
Spherical agg lomerate with PVP
polymer; (D) Nabumetone Spherical agglomerate with Sodium alginate polymer.

Fig 3:

DSC Thermograms of (A) Nabumeto ne, Pure drug (B) spherical agglomerates of Nabumeto ne, (C) Na bumetone
Spherical ag glomerates with PVP po lymer (D) Nabumetone Spherical agg lomerates with sodium alginate polymer

Page 161

Pradnya Patil et al. IRJP 2012, 3 (1)

Fig 4: XRD analysis of (A) Pure drug Nabumetone; (B) PVP K-30 Spherical agglomerates of Nabumetone; (C)
Sodium alginate spherical
agglomerates of Nabumetone

Fig 5: SEM analysis of A) Nabumetone pure drug; B)Spherical agglomerate of Nabumetone of 1 00


magnification;X(C,D,E,) Spherical agglomerate
of Nabumetone with polymer 1% PVP k-30 with magnification 135x, 36x,160x

Page 162

Figagglomerates;
5: Cu mulative
(B)Percent
PVP Nabumetone
Drug Release
spherical
alginate
of
Nabumetone
agglomerates
Sodium
(A)Source
Algof
spherical
ininate
support:
different
Nabu
agglomerates
Nil,
concentrations
metone
Co nflict
Spherical
with
ofwith
interest:
pure
Agglomerates
pure
drugdrug
None
andand
Plain
Declared
in Plain
different
agglomerates
agglomerates;
concentrations with 1%
pure
PVP
drug
and
and
sodium
(Plain
C)