FORMULATION DEVELOPMENT AND EVALUATION OF

Academic Sciences
International Journal of Pharmacy and Pharmaceutical Sciences
ISSN- 0975-1491
Vol 5, Suppl 3, 2013
Research Article
FORMULATION DEVELOPMENT AND EVALUATION OF VENLAFAXINE HCl SUSTAINED
RELEASE MATRIX TABLET
RAHUL THORAT1, PURUSHOTTAM PATIL*1, RASHMI AAGE2, PRASHANT PURANIK1, VIRAJ SALVE1
1Govt.College
of Pharmacy, Aurangabad. 431005, 2Y. B. Chavan College of Pharmacy, Aurangabad. 431001 (M.S) India.
Email: [email protected]
Received: 27 Jun 2013, Revised and Accepted: 30 July 2013
ABSTRACT
Objectives: The purpose of research work is to prepare Sustained Release Dosage Form (SRDF) of Venlafaxine HCl. As its half life is 5-6 Hrs and
having good solubility (BCS Class I) it is suitable candidate for sustained release tablet dosage form.
Method: It was formulated to matrix tablet by direct compression method using Carbopol 971P and Ethyl cellulose as sustaining polymers.
Differential Scanning Calorimetry (DSC) study shows that drug and other excipients are compatible with each other. The effects of polymers
concentration on drug release profile were investigated. A 3 2 full factorial design was applied to systemically optimize the drug formulation.
Concentration of Carbopol 971P and Ethyl cellulose are selected as independent variables and % Cumulative release of drug for 3 and 24 hrs
(Q3,Q24) were selected as dependent variables.
Results: All precompressional and post compressional parameters were within official limit. Batch F5 containing Carbopol 20% and Ethyl cellulose
(20cps) 10 % shows drug release upto 95.47 % in 24 Hrs selected as optimized batch. ANOVA data shows models were significant. Drug release
kinetics study shown that it follows Korsmeyer Peppas model (r2=0.9922) and release exponent (n=0.4365) shows mechanism is Fickian type.
Conclusion: Hence by formulating its sustained release matrix tablets of 24 Hrs creates new hope for patient as improving patient compliance and
decreasing frequency of administration.
Keywords: Sustained release matrix tablet, Venlafaxine HCl, Carbopol 971P, Ethyl cellulose etc.
INTRODUCTION[1-7]
SRDF provides the initial release of the drug sufficient to provide a
therapeutic dose soon after administration and then a gradual
release over an extended period. Recently, SRDF became a very
useful tool in medical practice offering a wide range of actual and
perceived advantages to the patients. The basic rational for
sustained drug delivery is to alter the drug release and also to
formulate such dosage form that improves patient compliance. To
target chronic diseases it is the best suitable dosage form.An
appropriate formulation can make the absorption, distribution,
metabolism and elimination (ADME) profile of a drug much more
favourable. Venlafaxine HCl is an orally active serotonin
noradrenalin reuptake inhibitor used in the treatment of major
depressive disorders. The successful treatment of depression
depends on the maintenance of effective drug concentration level
in the body for which a constant and uniform supply of drug is
desired. It is a highly water soluble drug (Class I) with the
biological half life of 5 Hrs thus requires two to three time daily
dosing to maintain plasma drug concentration. So providing its
slow release to maintain therapeutic level is the major need of this
formulation.
MATERIALS AND METHODS
Digital melting point apparatus. (Veego Digital Melting point
apparatus) The melting point was recorded.
2) UV Spectrum and Calibration curve of Venlafaxine HCl
The UV spectrum of Venlafaxine HCl was obtained using Shimadzu
UV1700. Accurately weighed 25 mg of the drug was dissolved in
sufficient quantity of buffer pH 6.8 and volume made upto 25 ml
known as stock solution (1000 µg/ml). 1ml of aliquot was
withdrawn and volume was made upto 100 ml using buffer pH 6.8 to
obtain the concentration of 10µg/ml. Subsequently aliquots were
removed to give 2-10µg/ml. The resultant solution was scanned
from 400 to 200 nm.
3) Fourier Transform Infra-Red Spectra (FTIR)
The drug sample was placed in FTIR cuvette. The drug sample was
scanned over the range of 4000-400 cm-1on an FTIR (Prestige 21
SHIMADZU). The FTIR spectra of drug sample were recorded.
Similarly, the procedure repeated by dispersing a sample {drug, drug
and polymer (1:1) as well as mixture of drug and polymers
(1:1:1:1)} in FTIR cuvette.
4) Differential Scanning Calorimetry (DSC)
Venlafaxine HCl was received as a gift sample from Lupin Research
Park, Aurangabad. Ethyl cellulose was gifted from Colorcon Asia Pvt
ltd, Goa. MCC PH102 was obtained from Signet Chemicals, Mumbai.
Carbopol 971P, PVP K30, Magnesium stearate, Talc were purchase
from Dipa Chemicals, Aurangabad. All other chemical and reagent
were of analytical grade.
The thermal behaviour of Venlafaxine HCl was studied using
Shimadzu DSC TA60 WS Thermal Analyzer. Accurately weighed
samples of (For drug 6.06 mg) were hermetically sealed in
aluminium pan and heated at a constant rate of 20°C/min over
temperature range of 100 to 300°C. The DSC thermogram was
recorded. The physical mixtures of drug with polymers for
compatibility studies were prepared by triturating drug and drug
and polymers (1:1) in a dried mortar for 5 min and kept as it is for
24 hrs.
Methods
B) Preparation of Tablet[24-25]
A) Drug identification and drug-excipients compatibility
study[8-23]
Matrix tablets of Venlafaxine HCl were prepared by direct
compression method using 10 mm flat-faced punch 10mm of 12
stations (Lab Press Machinery Pvt. Ltd, Ahmadabad, India.) The
active ingredient and the excipients were passed through 60 mesh
sieve and thoroughly mixed using a polybag for 10 minutes. PVP K30
was used as binding agent and magnesium stearate, talc were added
Materials
1) Melting Point
Melting point of Venlafaxine HCl was determined by taking a small
amount of sample in a capillary tube closed at one end and placed in
Patil et al.
Int J Pharm Pharm Sci, Vol 5, Suppl 3, 757-765
to the above blend as flow promoters and further mixed for another
10 minutes. In all the formulations the amount of Venlafaxine HCl
was kept constant (75mg) Table 1 shows different matrix tablets of
Venlafaxine HCl using Carbopol 971P and Ethyl cellulose.
Table 1: Formulation of 32 Factorial Design Batches
Ingredients (mg) / batch
Venlafaxine HCl
Carbopol 971P
Ethyl cellulose
(20cps)
PVP K30
MCC 102
Mg. Stearate
Talc
Total
F1
75
45
15
F2
75
45
30
F3
75
45
45
F4
75
60
15
F5
75
60
30
F6
75
60
45
F7
75
75
15
F8
75
75
30
F9
75
75
45
9
146
5
5
300
9
131
5
5
300
9
116
5
5
300
9
131
5
5
300
9
116
5
5
300
9
101
5
5
300
9
116
5
5
300
9
101
5
5
300
9
86
5
5
300
C) Evaluation of flow properties for Factorial blend[26-32]
2) Weight variation test
The quality of tablet depends upon the quality of powder from which
it is prepared. The powder of factorial batches were evaluated for
Bulk density, Tapped density, Carr’ index (compressibility), Angle of
repose and Hausner’s ratio. The evaluated parameters of powder are
reported in the Table 4.
Five tablets were taken and average weight of the tablet was
determined. The tablets were weighed individually and the weight
variation was determined
1) Bulk density
Tablet hardness is defined as force required to crushing the tablet in
diametric compression test. The hardness was measured with
Monsanto hardness tester.

Apparent bulk density ( b) was determined by pouring the blend
into a graduated cylinder. The bulk volume (Vb) and weight of the

powder (M) was determined. The bulk density ( b) was calculated
using following formula:
Bulk Density = M / Vb
2) Tapped density
The measuring cylinder containing a known mass of blend (M)
was tapped for a fixed time (100 tapping). The minimum volume
(Vt) occupied in the cylinder and weight of the blend was
measured. The tapped density (
following formula.
 t)
was calculated using
Tapped Density = M / Vt
3) Carr’s index
The Carr’s index is expression that shows the compressibility of the
powder. It is calculated by using the formula,
Carr’s Index = [(Tapped Density – Bulk Density) / Tapped Density] x
100
4) Hausner’s ratio
The Hausner’s ratio (H) is an indication of flowability of the powder.
It is calculated by the formula,

t
b
3) Hardness
4) Friability
Twenty tablets were weighed and subjected to friability test in
Roche friabilator. The pre-weighed sample was placed in friabilator
which revolves at 25 rpm for 4 min. dropping the tablets through a
distance of 6 inch with each revolution. This process was repeated
for all formulations and the percentage friability was calculated.
5) Drug content
Randomly selected 1 tablet from each batch was crushed in a mortar
and pestle. The crushed powder equivalent to 100 mg of Venlafaxine
HCl was taken and dissolved in 100 ml of buffer pH 6.8 (1000µg).
Then filtered through Whattman filter paper No 42. The
concentration of Venlafaxine HCl was determined by measuring the
absorbance at 225nm. Aliquots were taken from stock solution and
diluted with buffer pH 6.8 and analyzed by UV-Visible
Spectrophotometer (UV-1700 SHIMADZU).
6) In vitro drug release study[33-37]
The drug release rate from Venlafaxine HCl SR matrix tablets (n=3)
was determined using USP apparatus type II (Labindia, India). The
dissolution test was performed using 900 ml of 0.1N HCl for first 2
Hrs and then buffer pH 6.8 for remaining 22 hrs at 37  0.5C and 50
rpm. The drug release and drug release kinetics was calculated by
PCP disso ver. 3.0. The cumulative drug release of all 9 batches is
reported in the Tables 6 and Fig. 6 resp.
E) Statistical analysis by Design Expert Software
It is a maximum angle possible between the surface of pile and
the horizontal plane. The lesser the angle of repose, more is the
free flowing powder and vice-versa. The angle of repose for the
powder of each formulation was determined by the method.
A 32 full factorial design was selected and the 2 factors were
evaluated at 3 levels, respectively. The percentages of Carbopol
971P (X1), Ethyl cellulose (X2) were selected as independent
variables and the dependent variables were Q3, Q24. The data
obtained were treated using Stat Ease Design Expert 7.1.6 software
and analyzed statistically using analysis of variance (ANOVA) (Table
7, 8). The data were also subjected to 3-D response surface
methodology to study the interaction of Carbopol 971P (X1), Ethyl
cellulose (X2) on dependent variables. (Fig. 7, 8)
D) Evaluation of Tablets
F) Kinetics analysis of drug release
Tablets are evaluated for following official and non official tests.
To analyze the mechanism of drug release from the tablet the In vitro
dissolution data were fitted to zero order, first order, Higuchi release
model, Hixson and Crowell powder dissolution method and
Korsmeyer Peppas model by using PCP Disso Version 3 software,
and the model with the higher correlation coefficient was considered
to be the best model. The observations summarized in the Table 9.
5) Angle of repose
1) Appearance
The appearance, colour and any other flaws like chips, cracks,
surface texture etc. are other important morphological
characteristics were observed.
758
Patil et al.
Int J Pharm Pharm Sci, Vol 5, Suppl 3, 757-765
RESULTS AND DISCUSSION[38-50]
A) Drug Identification and drug-excipients compatibility study
1) Melting Point
The melting point of Venlafaxine HCl was determined on Digital
melting point apparatus was found to be 213º-216ºC which is in
good agreement with reported melting point.
2) UV Spectrum and Calibration curve of Venlafaxine HCl
The UV spectrum of Venlafaxine HCl solution (10µg/ml) exhibited
wavelength of absorbance maximum at 225 nm which complies with
the reported and calibration curve shows r2=0.999
3) Fourier Transform Infra Red Spectrophotometer (FTIR)
In all physical mixtures of drug and polymer, there was neither
masking of single characteristic peak nor existence of additional
peak in the spectra. (Fig. 2, 3 and Table 2) so we can conclude that
drug and polymers are compatible with each other.
4) Differential scanning calorimeter (DSC)
The endothermic peak at 210.94ºC of blend can be attributed as that
of Venlafaxine HCl. (214.67 ºC) Thus the thermogram showed that
the Venlafaxine HCl, Carbopol 971P, Ethyl cellulose are compatible
with each other since there is no significant difference in
endothermic peak of pure drug (Table 3) and physical mixture of
drug with other excipients.
C) Evaluation of flow properties for Factorial blends
1) Bulk density
The bulk density of powder is important parameter in the
compressibility of the powder. The bulk density was between 0.410
to 0.437gm/cm3.
2) Tapped density
The tapped density of powder is important parameters in the
compressibility of the powder. The tapped density was found to be
0.497 to 0.567 gm/cm3.
3) Carr’s index
The Carr’s index is indicator of compressibility. The value below 21
% shows fair to passable compressibility. It was found to be 16.32 to
23.50 %.indicating passable compressibility.
0.35
Absorbance
0.3
0.25
0.2
0.15
0.1
0.05
0
0
2
4
6
Conc. ug/ml
8
10
12
Fig. 1: UV Spectrum and Calibration curve of Venlafaxine HCl
759
Patil et al.
Int J Pharm Pharm Sci, Vol 5, Suppl 3, 757-765
Fig. 2: FTIR spectrum of Venlafaxine HCl
Fig. 3: FTIR spectrum of Factorial tablet
Table 2: Fourier Transform Infrared spectral assignments with excipients
S. No.
1
2
3
4
Functional Group
OH
C6H5
Aliphatic CH
C-O-C
Reported Values
3300-3400
1500-1600
2800-3000
1000-1200
Venlafaxine HCl
3321.42
1514.12
2943.37
1039.63
Factorial Tablet
3321.42
1514.12
2936.21
1039.63
760
Patil et al.
Int J Pharm Pharm Sci, Vol 5, Suppl 3, 757-765
DS C
mW
Temp
C
Thermal Analysis Result
10.00
Venlaflaxine.tad
Venlaflaxine.tad
[Temp Prog ram]
Start Temp 100.0
Temp Rate Hold Temp Hold Time
[C/min ]
[ C ]
[ min ]
20.00
300.0
0
Temp
DSC
300.00
0.00
File Name:
Detector:
Acq uisition Date
Acq uisition Time
Sample Name:
Sample Weig ht:
Annotation:
-10.00
Venlaflaxine.tad
DSC60
12/11/08
12:55:56
Venlaflaxine
6.060[mg ]
200.00
-20.00
-30.00
0.00
Start
205.85 0
C
x10
End
223.09 0
C
x10
Peak
214.67 0
C
x10
Onset
210.17 0
C
x10
Endset
0
220.41 x10
C
Heat
0
-640.29 x10
mJ
-105.66 0
x10
J/g
Heig ht
-30.98 0
mW
x10
100.00
5.00
10.00
Tim e [m in]
Fig. 4: DSC Thermogram of Venlafaxine HCl
DSC
mW
Temp
C
Thermal Analysis Result
V+Blend.tad Temp
V+Blend.tad DSC 300.00
[Temp Prog ram]
Start Temp 100.0
Temp Rate Hold Temp Hold Time
[C/min ]
[ C ]
[ min ]
30.00
300.0
0
0.00
File Name:
Detector:
Acq uisition Date
Acq uisition Time
Sample Name:
Sample Weig ht:
Annotation:
V+Blend.tad
DSC60
13/02/07
14:50:30
V+Blend
11.360[mg ]
200.00
-10.00
-20.00
0.00
2.00
Start
0
187.39 x10
C
End
221.25 0
C
x10
Peak
210.94 0
C
x10
Onset
201.99 0
C
x10
Endset
0
216.63 x10
C
Heat
0
-278.64 x10
mJ
-24.53 0
J/g
x10
Heig ht
0
-12.64 x10
mW
4.00
Tim e [m in]
100.00
6.00
8.00
Fig. 5: DSC Thermogram of physical mixture
Table 3: DSC compatibility of drug and mixture
S. No.
1
Parameters
Peak obtained oc
Venlafaxine HCl
214.67
Physical Mixture
210.94
Table 4: Powder Flow properties of factorial batches
Batch
F1
F2
F3
F4
F5
F6
F7
F8
F9
Bulk Density
(gm/cm3)
0.423± 0.26
0.419± 0.07
0.437±0.19
0.417± 0.01
0.413± 0.06
0.420± 0.21
0.431± 0.01
0.428± 0.17
0.41± 0.01
Tapped Density
(gm/cm3)
0.512± 0.19
0.499± 0.07
0.567±0.01
0.494± 0.05
0.497± 0.36
0.527± 0.005
0.521± 0.013
0.535± 0.028
0.536± 0.031
Carr’s Index
(%)
17.38± 1.09
16.32±1.78
22.92± 1.02
16.59± 1.35
16.90± 1.81
20.30± 2.13
17.27± 1.23
20.00± 1.62
23.50± 1.26
Hausner’s Ratio
Angle of Repose (0)
1.21± 0.09
1.19± 0.04
1.24± 0.08
1.18± 0.048
1.20± 0.126
1.25± 0.043
1.20± 0.094
1.25± 0.060
1.30± 0.041
27.12± 1.21
29.24± 1.05
25.36± 1.29
25.12± 1.01
26.42± 1.23
28.54± 1.12
27.18± 1.32
29.36± 1.14
27.48± 1.26
All values are mean±SD, n=3
761
Patil et al.
Int J Pharm Pharm Sci, Vol 5, Suppl 3, 757-765
4) Hausner’s ratio
4) Friability
The Hausner ratio is another parameter indicating the flow
properties. It was found to be 1.18 to 1.30 indicating good to
passable flowability.
The friability is important characteristics to be evaluated for
handling and transportation properties of the tablets. The friability
of tablets was less than 0.5% which indicates good handling and
transportation characteristics.
5) Angle of repose
5) Drug content
The angle of repose can be correlated with type of flow of powder.
The angle of repose 20 to 30º indicates the good flow while the angle
of repose more 30º indicates poor flow properties and angle of
repose below 20º indicates excellent flow properties. The angle of
repose was found to be within the range of 25.12º to 29.36º
indicating good flowability.
The drug content of the nine formulations was found to be between
97.22 to 101.89% (i.e. variation of ±4%). The value ensures good
uniformity of the drug content in the tablet.
6) In vitro drug release studies
In vitro drug release study was carried out using USP dissolution
apparatus II in 0.1N HCl for first 2 Hrs and then buffer pH 6.8 for a
period of remaining 22 Hrs.
D) Evaluation of Tablets
The tablets from the factorial batches were evaluated for different
evaluation parameters of tablets.
The formulations F5, F6 and F8 comprising of Carbopol 971P 60mg,
60mg, 75mg resp. and Ethyl cellulose 30 mg, 45 mg, 30 mg resp.
showed improved drug release upto 24 hrs and minimum burst
release with more than 80% release in 24 hrs. Hence formulation with
comparatively lower polymer concentration (F5) was selected as
optimized formulation. Formulation containing combination of
Carbopol 971P and Ethyl cellulose retarded the drug release upto 24
Hrs, but showed 41 to 50% drug release in first 3 Hrs in initial batches
which were not appropriate. This burst release may be due to high
water solubility of drug and more time required for wetting of tablet.
This problem was overcome by increasing the Conc. of Polymers.
1) Appearance
The tablets from all factorial batches were white, circular. The
surface texture was smooth. The thickness of tablets of factorial
batches was 3.12 to 3.24 mm and it was found to be within limit of
deviation from average value (not more than 5%).
2) Weight variation
For tablet weighing 300 mg or more, not more than two tablets
differ from the average weight by 5% deviation. The weight
variation within limits indicates uniformity in tablet compression
and consequently content of drug in a unit.
E) Statistical analysis by Design Expert Software
i) ANOVA study
3) Hardness
The Q3, Q24 for the 9 batches (F1-F9) showed a wide variation (i.e.,
35.32-50.28% and 84.69-102.37% resp). Data clearly indicates that
the Q3, Q24 values are strongly dependent on the selected
independent variables. The coefficients of X1 X2 were found to be
significant at p <0.05, hence confirmed the significant effect of all the
variables on the selected responses.
The hardness is important characteristics to be evaluated for
handling and transportation properties of the tablets. The hardness
of tablets was found to be 6.3 to 8.0 Kg/cm2which indicate good
handling and transportation characteristics.
Table 5: Evaluation of Venlafaxine HCl SR matrix tablets
Batch
Appearance
F1
F2
F3
F4
F5
F6
F7
F8
F9
White, circular, 10mm
White, circular, 10mm
White, circular, 10mm
White, circular, 10mm
White, circular, 10mm
White, circular, 10mm
White, circular, 10mm
White, circular, 10mm
White, circular, 10mm
Weight variation*
mg ± SD
300±0.47
300±0.81
300±1.69
299±1.24
300±0.47
300±1.24
300±0.94
300±81
300±0.47
Hardness (Kg/cm2)
±SD
6.3±0.28
6.7±0.5
7±0.31
7.3±0.21
7.6±0.28
8±0.5
7.5±0.28
7±0.5
7.8±0.5
Friability# %
0.61±0.02
0.71±0.04
0.65±0.09
0.50±0.03
0.49±0.06
0.57±0.09
0.69±0.07
0.82±0.03
0.78±0.07
Thickness (mm)
±SD
3.18±0.12
3.20±0.220
3.18±0.03
3.20±0.13
3.24±0.11
3.20±0.12
3.18±0.25
3.12±0.15
3.16±0.03
Drug content (%mg)
±SD
99.03±0.14
97.03± 1.11
100.02±0.45
99.5±0.79
98.5±0.49
98.1± 0.49
101.89± 0.83
97.22± 0.36
98.62± 0.52
* n=20, #n=10, All values are mean ± SD
[
Table 6: Percent cumulative drug release of formulation F1 to F9
Time (Hrs)
0.5
1
2
3
4
6
8
12
16
24
Cumulative Drug Release (%)
F1
F2
F3
14.07
10.76
14.25
±0.10
±0.03
±0.06
23.42±0.09
16.96±0.10
19.85±0.09
37.60
30.98
29.90
±1.44
±0.04
±1.43
50.02±1.40
47.52±0.02
41.73±1.53
67.57
55.67
48.02
±1.50
±0.09
±1.37
73.36
61.87
62.29
±1.13
±0.08
±1.27
79.85±1.32
67.16±0.27
71.47±1.20
83.74
74.36
78.65
±1.40
±0.35
±1.22
91.17±1.66
87.49±0.40
86.03±1.19
102.3±1.54
97.37±0.28
93.28±1.37
F4
11.70
±0.14
18.42±0.13
29.81
±0.01
50.28±0.12
57.23
±0.05
64.37
±0.08
70.47±0.02
73.73
±0.24
83.42±0.01
99.33±0.06
F5
16.60
±0.12
21.95±0.06
28.61
±0.07
38.14±0.19
49.99
±0.20
57.13
±0.16
71.40±0.12
76.31
±0.60
82.34±0.14
95.47±0.32
F6
8.094
±0.05
15.43±0.11
22.50
±0.15
36.82±0.10
41.66
±0.22
57.80
±0.11
66.20±0.38
72.91
±0.25
82.17±0.27
86.83±0.37
F7
13.73
±0.07
22.66±0.12
32.08
±0.14
42.73±0.24
45.07
±0.03
54.82
±0.15
73.92±0.17
80.88
±0.01
86.64±0.09
93.23±0.14
F8
10.53
±0.04
15.38±0.11
29.88
±0.05
38.08±0.05
44.12
±0.19
53.90
±0.08
72.95±0.06
77.49
±0.22
84.36±0.44
89.81±0.14
F9
9.547
±0.07
16.51±0.14
22.57
±0.13
35.32±0.37
47.66
±0.03
52.28
±0.07
65.36±0.34
75.41
±0.25
79.74±0.41
84.69±0.26
All values are mean ± SD, n=3
762
Patil et al.
Int J Pharm Pharm Sci, Vol 5, Suppl 3, 757-765
Fig. 6: Percent cumulative drug release of formulation F1 to F9
Table 7: Analysis of variance for Q3
Source
Model
A-C
B-EC
Residual
Cor total
R Squared
Adj R-Squared
Pred R-Squared
Adeq Precision
Sum of Squares
237.81
92.28
145.53
33.25
271.06
0.8773
0.8364
0.7853
13.018
Degrees of Freedom
2
1
1
6
8
-
Mean Square
118.91
92.28
145.53
5.54
-
F Value
21.45
16.65
26.26
-
P Value
0.0018
0.0065
0.0022
-
Model Significant/Non Significant
P Value
0.0147
0.0069
0.0042
Model Significant/Non Significant
Significant
Table 8: Analysis of variance for Q24
Source
Model
A-C
B-EC
R- Squared
Adj R- Squared
Pred R- Squared
Adeq Precision
Sum of Squares
260.05
106.60
151.30
0.9729
09279
0.7082
14.574
Degrees of Freedom
5
1
1
Mean Square
52.01
106.60
151.30
F Value
21.58
44.23
62.78
Significant
Design-Expert® Software
Factor Coding: Actual
diso 3hr
Design points above predicted value
Design points below predicted value
50.41
35.32
X1 = A: c
X2 = B: ec
d is o 3 h r
55
50
45
40
35
30
75.00
45.00
69.00
39.00
63.00
33.00
57.00
27.00
B: ec
51.00
21.00
A: c
15.00 45.00
Fig. 7: Response surface plot for Q3
763
Patil et al.
Int J Pharm Pharm Sci, Vol 5, Suppl 3, 757-765
Design-Expert® Software
Factor Coding: Actual
diso 24hr
Design points above predicted value
Design points below predicted value
102.37
84.69
d is o 2 4 h r
X1 = A: c
X2 = B: ec
105
100
95
90
85
80
75.00
45.00
69.00
39.00
63.00
33.00
57.00
27.00
B: ec
A: c
51.00
21.00
15.00
45.00
Fig. 8: Response surface plot for Q24
Table 9: Model fitting data of Venlafaxine HCl SR matrix tablet (Optimized batch F5)
S. No.
Formulation
1
F5
Models
Zero Order
First Order
Matrix
Korsmeyer Peppas
Hixon Crowell
R
0.5964
0.9566
0.9754
0.9922
0.8866
ii) 3-D Response surface plot
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The response surface plots showed that various combinations of
independent variables X1, X2 may satisfy any specific requirement
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1.
F) Kinetics analysis of drug release
The results shown that the factorial design batches follows Korsmeyer
Peppas model. The R value of Korsmeyer Peppas was found close to one
(0.9922) the slow release of the drug from the matrix may be due to the
formation of viscous gel of Carbopol 971P. The n values were found to be
less than 0.5 (0.4365) indicating that the mechanism is diffusion
controlled or Fickian type as shown in Table 9.
CONCLUSION
The drug has elimination half life of 5(±2) hours shows that it is a
suitable candidate for sustained release formulation. Advantage of
this formulation over others is that it is easy to prepare and cost
effective. Optimum concentration of Carbopol 971P and Ethyl
cellulose based formulations was found to provide the desired
release (95.47%) with a reduced frequency of administration.
Release Kinetics shows it follws Korsmeyer Peppas model and
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type tablet of Venlafaxine Hydrochloride meant for once-a-day
administration.
ACKNOWLEDGEMENT
The authors are grateful to Lupin Research Park, Aurangabad for
providing Venlafaxine HCl as gift sample and Dr. S.S. Khadabadi
Principal Goverment College of Pharmacy, Aurangabad for necessary
support and valuable guidance.
N
K
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