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Article Received on: 01/11/11 Revised on: 2 1/12/11 Approved for publication: 09 /01/12
17
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
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
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
NS4
0.237 0.0005
1.11 0.005
1.07 0.005
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
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
p < 0 .0 5).
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
Spherical
Agglomerates
NS1
SLS (2%,
Nabumetone Released
(% )
1 00.0 0.0 (after 3h)
MDT (min)
b
b
15.81 0.11
14.22 0.35
NS4
13.13 0.10
NP1
NP2
13.91 0.11
13.44 0.30
NP3
13.16 0.31
NP4
11.10 0.16
14.47 0.29
13.68 0.11
16.58 0.21
NS2
NS3
DRUG
SP
m /V)
bImprovements
Page 160
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
Fig 4: XRD analysis of (A) Pure drug Nabumetone; (B) PVP K-30 Spherical agglomerates of Nabumetone; (C)
Sodium alginate spherical
agglomerates of Nabumetone
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)