Jurnal Carbamazepin
Jurnal Carbamazepin
Jurnal Carbamazepin
Fasiuddin Arif Mohammed. et al. / International Journal of Biological & Pharmaceutical Research. 2012; 3(1): 145-153.
IJBPR
ABSTRACT
The objective of this research work was to formulate and evaluate the extended release tablets containing 200mg of
Carbamazepine. Different excipients were tested for their compatibility with Carbamazepine, which revealed that there is no
physical and chemical interaction occurred. Extended release tablets were formulated by Wet Granulation method incorporating
HPMC K4M, a hydrophilic polymer, Dicalcium phosphate (Anhydrous) as diluent, Povidone (K-30) as Binder, Colloidal
silicon dioxide (Aerosil-200) as Glidant, Hydrogenated Castor Oil (Boricin Pharma) and Talc as lubricants. Dissolution profiles
were studied in Purified water as dissolution medium (900ml). The drug release were estimated at 3, 6, 12 and 24 hours by
Ultra violet Visible spectrophotometer (UV 1601, Shimadzu), at 284 nm. The influence of variables like polymer type, drug:
polymer ratio on Carbamazepine profile release was studied. The release mechanisms of Carbamazepine extended release
tablets were evaluated. The thickness, hardness, friability, weight variation and drug content of the formulated extended release
tablets were evaluated. Based on the evaluation results, T9 (10% Methocel K4M) formulation was selected as the best
formulation, reproducibility trials were taken and the results were found to be satisfactory.
Key Words: Carbamazepine, Hydroxy Propyl Methyl Cellulose (HPMC K4M), Wet Granulation method, Extended release
drug delivery and Evaluation.
INTRODUCTION
Oral administration of drugs has been the most
common and preferred route for delivery of most
therapeutic agents. It remains the preferred route of
administration investigated in the discovery and
development of new drug candidates and formulations. The
Corresponding Author
Fasiuddin Arif Mohammed
Email: [email protected]
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MANUFACTURING PROCESS
The Manufacturing procedure to formulate
Carbamazepine extended release tablets USP 200mg
consists of the following steps: (Kuksala et al., 2006;
Owen et al., 2006)
1. SIFTING: Sift Carbamazepine through #80 mesh, Sift
Methocel K4M,Dicalcium phosphate (Anhydrous),
HPMC 5CPs through #40mesh.
2.
3.
4.
5.
6.
7.
8.
METHODS
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Pi = m/Vo
Where,
m : Mass of the blend
Vo: Untapped Volume
Tapped Density
Procedure
Weighed quantity of Carbamazepine granules was
taken into a graduated cylinder, volume occupied by
granules was noted down. Then cylinder was subjected to
500/ 750 and 1250 taps in tapped density tester (Electro
Lab USP II) According to USP , the blend was subjected
for 500 taps the % Volume variation was calculated by
following formula.
Where,
Pt = m/Vi
CI=Vo-Vi/V*100
Where, Vo : Untapped density
Vi: Tapped density
HAUSNERS RATIO
It is measurement of frictional resistance of the
drug. The Ideal range should be 1.2 -1.5. It was determined
by the ratio of tapped density to bulk density.
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Hardness test
Hardness indicates the ability of a tablet to
withstand mechanical shocks while handling. The hardness
of tablets was determined by using Monsanto hardness
tester. It is expressed in kg/cm2. Three tablets were
randomly picked and hardness of tablets was determined.
(Values are given in Table 7)
Limits: 4 10 kg/cm2
Friability test
Friability of the tablets is determined by using Roches
friabilator. It is expressed in %. Ten tablets were initially
weighed and transferred to friabilator. The friabilator is
operated at 25 Rpm for 4 min or run upto100 revolutions,
the tablets are weighed again. The % friability of tablets
was then calculated. (Values are given in Table 7)
Limits: The Friability of tablet should not be exceed 1%
Initial wt Final wt
F
=
_________________
X 100
Initial wt
Weight variation test
Ten tablets were selected randomly from each batch
and weighed individually to check for weight variation. A
little weight variation is allowed by U.S pharmacopeia.
The following % weight variation is allowed (Ikinci G et
al., 1999; Vidyadhara S et al., 2003). (Values are given in
Table 5)
CONTENT OF UNIFORMITY
Standard preparation
Weigh accurately about 0.1g of Carbamazepine
WS in to a 50ml volumetric flask, add 30ml of methanol,
shake and sonicate to dissolve the content, makeup the
volume with methanol. Filter the solution through
membrane filter. Pipette out 5 ml of the above solution in
to a 100 ml volumetric flask and makeup the volume with
methanol. Further, pipette out 5ml of the above solution in
to a 50ml volumetric flask and makeup the volume with
methanol.
Sample preparation
Randomly select 10 tablets. Finally powder one
tablet and transfer quantitatively the powdered tablet into a
100ml volumetric flask. Add 70ml of methanol shake by
mechanical means for 60 minutes; sonicate for 15 minutes
and makeup the volume with methanol. Allow to stand for
10 to 15 minutes, and then filter the portion of the
supernatant solution through a membrane filter. Pipette out
5 ml of the above solution into a 100 ml volumetric flask
and makeup the volume with methanol. Further, pipette out
5 ml of the above solution into a 50 ml volumetric flask
and make up the volume with methanol.
PROCEDURE
Measure the absorbance of the Standard preparation
and sample preparation using suitable UVVisible
spectrophotometer at about 284nm using methanol as
blank. Calculate the release of Carbamazepine in
percentage with respect to the label claim by using the
following expression.
AT X WS X 5 X 5 X 100 X 100 X 50 X P
100
_______________________________________ X 1000 X__________
AS X 50 X 100 X 50 X 1 X 5 X 5 X 100
200
= % of Carbamazepine
1000
ii)
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Quantity/Tablet (mg)
T-6
T-7
T-8
T-1
T-2
T-3
T-4
T-5
T-9
T-10
T-11
T-12
201.59
201.59
201.59
201.59
201.59
201.59
201.59
201.59
201.59
201.59
201.59
201.59
97.50
89.38
81.25
73.12
65.00
56.87
48.75
40.63
32.500
32.50
32.50
32.50
6.250
3.91
12.03
20.16
28.29
36.41
44.54
52.66
60.78
52.660
68.91
68.91
68.91
10.00
10.00
10.00
10.00
10.000
10.00
10.00
10.00
10.00
10.000
10.000
10.000
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
5.00
5.00
5.00
5.00
5.00
5.00
5.00
5.00
5.00
5.000
5.000
5.000
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.000
2.000
2.000
5.00
5.00
5.00
5.00
5.00
5.00
5.00
5.00
5.00
5.000
5.000
5.000
325.00
325.00
325.00
325.00
325.00
325.00
325.00
325.00
325.00
325.00
325.00
325.00
Flow characters
Excellent
Good
Fair
Passable
Poor
Very Poor
Very Very Poor
Hausners ratio
1.00 1.11
1.12 1.18
1.19 1.25
1.26 1.34
1.35 1.45
1.46 1.59
> 1.60
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% variation
10
7.5
5
S.No
Drug+ Excipients
Parameter
Initial
value of
parameters
Carbamazepine
Any colour
change
No colour
change
Conditions
400C/75%RH
600C/90%RH
2
4
2
4
Week
Week
Week
week
No colour
No colour
No colour
No colour
change
change
change
change
Any colour
change
No colour
change
No colour
change
No colour
change
No colour
change
No colour
change
Any colour
change
Any colour
change
Any colour
change
No colour
change
No colour
change
No colour
change
No colour
change
No colour
change
No colour
change
No colour
change
No colour
change
No colour
change
No colour
change
No colour
change
No colour
change
No colour
change
No colour
change
No colour
change
Any colour
change
No colour
change
No colour
change
No colour
change
No colour
change
No colour
change
Any colour
change
No colour
change
No colour
change
No colour
change
No colour
change
No colour
change
2
3
4
5
6
Carbamazepine + Dibasic
calcium phosphate
(Anhydrous)
Carbamazepine+ HPMC
K4M
Carbamazepine+ HPMC 5
CPs
Carbamazepine+ Povidone
(K-30)
Carbamazepine + Iso
propyl alcohol &
methylene chloride
Carbamazepine + colloidal
silicon dioxide (Aerosil200)
carbamazepine+Talc
Any colour
change
No colour
change
No colour
change
No colour
change
No colour
change
No colour
change
Carbamazepine+
hydrogenated castor oil
(Boricin pharma)
Any colour
change
No colour
change
No colour
change
No colour
change
No colour
change
No colour
change
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Formulation
1
2
3
4
5
6
7
8
9
10
11
12
T1
T2
T3
T4
T5
T6
T7
T8
T9
T10
T11
T12
Bulk density
(g/cm3)
0.57
0.56
0.56
0.59
0.63
0.64
0.65
0.64
0.54
0.53
0.63
0.61
Tap density
(g/cm3)
0.65
0.64
0.63
0.69
0.76
0.78
0.75
0.75
0.62
0.60
0.71
0.68
Hausners
ratio
1.12
1.14
1.13
1.17
1.19
1.21
1.19
1.19
1.14
1.13
1.16
1.14
Compressibility
Index (%)
11.4
12.5
12.5
14.7
16.2
17.8
16.4
16.2
12.8
11.7
12.5
12.6
Angle of repose
(0 )
31.2
28.6
30.2
27.3
25.3
28.4
26.9
24.8
25.6
26.4
25.7
24.9
Moisture
Content (%)
0.81
0.79
1.02
1.06
0.97
0.84
0.96
0.82
0.93
1.09
1.06
0.92
Specification
Description
White, flat,
circular bevel
edged
uncoated
extended
tablets with a
break line on
one surface.
Identificati
on test
Passes for
carbamazepin
e
Complies
Complies
Complies
Complies
Complies
Complies
Complies
Complies
Complies
Complies
Complies
Complies
S.N
o.
Average
weight
321-329mg
(Taget
weight325mg)
325.2
324.9
324.5
325.2
325.5
324.8
325.1
324.6
324.9
323.8
325.4
324.2
3.6-4.0mm
3.80
3.72
3.68
3.89
3.72
3.90
3.84
3.78
3.72
324.6
324.9
323.8
T7
T8
T9
T10
T11
T12
Complies
Complies
Complies
Complies
Complies
Complies
Content
Uniformity
T6
Complies
T5
Complies
Weight
Variation
T4
Complies
T3
Complies
T2
Complies
Thickness
(mm)
Hardness
(kg/cm2)
Friability
(%w/w)
Complies
T1
4.0-8.0
Kg/cm2
Not more than
1.0%
5% from
the avearge
weight
0.11
0.14
0.12
0.11
0.16
0.15
0.18
0.12
0.15
0.15
0.14
-2.5
to
+1.9
-2.5
to
+2.1
-2.4
to
+1.8
-1.5
to +
2.8
-1.9
to
+2.4
-1.7
to
+3.1
-2.4
to
+1.8
-3.1
to
+2.5
-2.4
to
+1.9
-1.7
to
+2.7
-1.5
to
+2.2
0.08
-2.6
to
+1.9
85 to 115%
95%
98%
97%
98%
98%
99%
97%
96%
98%
98%
99%
98%
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Fasiuddin Arif Mohammed. et al. / International Journal of Biological & Pharmaceutical Research. 2012; 3(1): 145-153.
Specification
T1
T2
T3
T4
T5
T6
T7
T8
T9
T10
T11
T12
3rd hour
Between 10%
to 35%
4.3
%
6.9
%
7.9
%
11.
0%
12.1
%
14.3
%
15.1
%
17.5
%
19.8
%
28.2
%
25.9
%
29.5
%
2.
6th hour
3.
12th hour
Between35%
to 65%
Between 65%
to 90%
15.8
%
32.3
%
16.
5%
39.
6%
18.
3%
43.
5%
20.
9%
48.
9%
23.4
%
53.9
%
28.5
%
60.5
%
33.9
%
63.9
%
35.6
%
68.0
%
33.5
%
79.9
%
50.2
%
78.7
%
48.9
%
73.1
%
51.3
%
75.6
%
4.
24th hour
NLT 75%
58.0
%
60.
8%
67.
5%
70.
9%
78.1
%
83.4
%
96.2
%
95.6
%
86.9
%
93.0
%
95.4
%
96.5
%
S.no
1.
DISCUSSION
To match the USP release profile of the drug, the
trial T10 was formulated with 10% of HPMC K4M, where
the release of drug at 3rd hour was found to be 29.5%
respectively, which meets the USP specification limits.
Hence reproducibility trials (T11 and T12) with the same
formula of T9 were taken to confirm whether it meets the
USP specification and it was found to be reproducible. The
release of drug depends not only on the nature of matrix
but also upon the drug polymer concentration. As the
percentage of polymer decreased from 30% to 10% the
release of drug was extended. The extended release tablets
were evaluated as per the USP specification and it was
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Fasiuddin Arif Mohammed. et al. / International Journal of Biological & Pharmaceutical Research. 2012; 3(1): 145-153.
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