ISSN No: 2321 – 8630, V – 1, I – 1, 2014
Journal Club for Pharmaceutical Sciences (JCPS) Manuscript No: JCPS/RES/2014/17, Received On: 03/08/2014, Revised on: 09/08/2014, Accepted On: 13/08/2014
RESEARCH ARTICLE Stability Indicating HPLC Method Development for Estimation of Montelukast Sodium and Acebrophylline in Combined Dosage Form Thesia DU1, Patel BP1 1 S. J. Thakkar College of Pharmacy, Avadh Road, Kalawad Road, Rajkot, Gujarat ABSTRACT Analysis of pharmaceutical product is very important as it concerned with life. Combination of Montelukast sodium and Acebrophylline is used in bronchial asthama and allergic rhinitis. In this Research work, Montelukast sodium and Acebrophylline stock solution was subjected to acid and alkali hydrolysis, oxidation, thermal photolytic and thermal degradation. In this Stability-Indicating method sample was analyzed by reverse phase C18 column (Hibar Lichrospher® 100, RP-18e 5 μm, 250 mm L × 4.6 mm diameter in size) as stationary phase and Acetonitrile:Methanol (60:40 %v/v, pH 3.2 adjusted with O-phosphoric acid) as a mobile phase at a flow rate of 0.8ml/min. Quantification was achieved at 260 nm with PDA detector. Method was validated according to ICH Q2 R1 guideline. The retention time for Montelukast sodium and Acebrophylline was found to be 15.49 minute and 3.45 minute, respectively. The linearity for Montelukast sodium and Acebrophylline was obtained in the concentration range of 5-25 µg/ml and 100-500 µg/ml with mean accuracies of 99.49-100.81% and 99.45-100.51% respectively. Values of %RSD for Precision Study and Robustness was found < 2%. % label claim was found to be 99.23% for MTKT and 100.83% for ACBR. The developed method meets all the acceptance criteria for the validation of analytical method as per the ICH Q2 R1 guideline. The degraded product peaks were well resolved from the pure drug peak with significant difference in their retentiontime values. A simple, precise and accurate stability indicating RP-HPLC method was developed for estimation of Montelukast sodium and Acebrophylline in combined Dosage form. KEYWORDS HPLC, Montelukast sodium, Montelukast, Acebrophylline, Stability Indicating HPLC, Degradation study, ACBR, MTKT INTRODUCTION
[3-[(1E)-2-(7-Chloro-2-quinolinyl)
Montelukast sodium (MTKT) 1-[[[(1R)-1-
ethenyl]
*Address for Correspondence: Purav Talaviya, S. J. Thakkar College of Pharmacy, Avadh Road, Rajkot, Gujarat. Email ID:
[email protected]
methylethyl) phenyl] propyl] thio] methyl]
phenyl]-3-[2-(1
hydroxy-1-
cyclopropaneacetic acid (Trade name: Singulair, Montair, Emlucast, Montek, Montelast, Monti) is a selective and orally active leukotriene receptor antagonist that
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99
inhibits the Cysteinyl leukotriene type-1
Though
individual
estimation
of
receptor (CysLT1) and blocks the action
Montelukast sodium was done by HPLC,
of Leukotriene D4 (and secondary ligands
Voltammetric,
LTC4 and LTE4) on the Cysteinyl
methods5-19
leukotriene receptor CysLT1 in the lungs
estimation was done by HPLC, HPTLC
and bronchial tubes by binding to it. It is
spectrophotometric
used for the treatment of asthma and to
method is available for the estimation of
relieve symptoms of seasonal allergies.1-3
Montelukast sodium and Acebrophylline
Spectrophotometric and
Acebrophylline methods.20-24
No
in their combined dosage forms. So it is Acebrophylline
1,2,3,6-
thought of interest to develop and validate
1,3-dimethyl-2,6-dioxo-7H-
chromatographic method for estimation of
Purine-7-aceticacid compound with trans-
these drugs in presence of degradation
4-[[(2-amino-3,5 dibromophenyl) methyl]
products in combined dosage form.
tetrahydro-
amino]
(ACBR)
cyclohexanol
(Trade
name:
cebofyl, AB phylline) is used in bronchial asthma
and
pulmonary
diseases.
It
contains Ambroxol and Theophylline-7acetic acid, the former facilitates the biosynthesis
of
while
raises
later
ambroxol,
by
pulmonary blood
stimulating
surfactant levels
of
surfactant
production. By deviating phosphatidyl choline
towards
surfactant
In proposed method, both the drugs are applied for forced degradation in acid, alkaline, oxidative, photolytic and thermal environment and these solutions were analysed by RP-HPLC method. Stress study was performed according to ICH guidelines for stability testing. Method was developed and validated according to ICH guidelines.
synthesis,
making it no longer available for the
After systematic and detailed study, the
synthesis of inflammatory mediators such
following procedures are recommended
as the leukotrienes, acebrophylline also
for the determination of Montelukast
exerts
sodium
an
inflammatory
effect.
Acebrophylline is obtained by targeted
and
Acebrophylline
in
pharmaceutical formulations.
salification of the Ambroxol base and Theophylline-7-acetic acid.4 This combination is launched by Alkem Healthcare Ltd. in market as brand name Abrofyl-M.
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MATERIALS & METHODS Montelukast sodium working standard grade was supplied by Torrent Research Centre,
Ahmedabad.
Acebrophylline
100
working standard grade was supplied by
a flow rate of 0.8 mL/min was carried out.
Ami Life science, Baroda. Acetonitrile,
The detection was monitored at 260 nm
methanol, water for Chromatography -
and injection volume was 20 μL. The peak
Lichrosolv® (Merck Specialities Pvt. Ltd.,
purity was checked with the photodiode
Mumbai), Ortho phosphoric acid 88% GR
array detector (PDA).
(Merck Specialities Pvt. Ltd., Mumbai),
Preparation of standard solutions and
Hydrogen peroxide (30%), LR grade
calibrations
(Merck, India), Sodium hydroxide AR
Standard stock solution of ACBR (2000
grade
ltd,
μg/mL) and MTKT (100 μg/mL) were
Mumbai), Hydrochloric acid 35% pure
prepared in methanol. To study the
AR
Ltd.,
linearity range, serial dilutions of ACBR
Sartorius Filter Paper 0.45
and MTKT were prepared from 100-500
micron (Sartorius, Germany) and Abrofyl-
μg/mL and 5-25 μg/mL in methanol and
M tablet formulation-Each tablet contains
injected
10 mg Montelukast sodium and 200 mg
construction of calibration curves, five
Acebrophylline manufactured by Alkem
standard solutions in concentration range
Laboratories was purchased from local
mentioned above were prepared and
market. Identification of both the drugs
injected on to column. Calibration curves
were done by interpreting the IR spectra
were prepared as concentration of drugs
of pure API of drug sample.
versus peak area response. The system
(Merck
(Merck
Mumbai),
specialties
specialities
Pvt
Pvt.
HPLC Instrumentation and Conditions The HPLC system consisted YL-Clarity 9100
HPLC
System
(YOUNG-LIN
INSTRUMENT, The Republic of Korea),
on
to
column.
For
the
suitability test was carried out from six replicates of standard solution of both the drug containing 100 μg/mL of ACBR and 5 μg/mL MTKT.
column heater and PDA detector (Waters
System
2998). Data collection and analysis was
Analysis of Formulations
performed using YL- Clarity software.
The SST ensures the validating power of
Separation
Hibar
the analytical method as well as confirms
Lichrospher® 100, RP-18e (5 μm), (250 ×
the resolution between different peaks of
was
achieved
on o
Suitability
Test
(SST)
and
4.6mm) columns maintained at 25 C using
interest. All critical parameters tested met
column oven. Isocratic elution with
the acceptance criteria on all days.
Methanol:Acetonitrile (40:60 %v/v), pH
Adequate resolution of ACBR and MTKT
adjusted to 3.2 with O-phosphoric acid at
peaks ensured the specificity of the
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101
method. The system suitability assessment
containing 100, 300 and 500 μg/mL of
for
ACBR and 5, 15 and 25 μg/mL of MTKT
the
analytical
established
HPLC
instrument
method
performance
were
used
for
precision
study.
parameters such as peak area, %RSD,
Repeatability study was determined by
Theoretical Plates (N) and Tailing factor
taking six replicates of ACBR (300
(Tf) for both the analytes. For analysis of
μg/mL) and MTKT (15 μg/mL). Assay
marketed formulations quantity of powder
method was evaluated with the recovery
from 20 tablets equivalent to 300 mg of
of the standards from excipients. Three
ACBR or 15 mg MTKT were weighed
different quantities (80%, 100% and
and transferred to a 100 mL volumetric
120%) of the standards were added to pre
flask containing about 20 mL of methanol,
analyzed formulation and were analyzed
ultrasonicated for 5 min and solution was
using the developed HPLC method.
filtered through Sartorius Filter paper No.
Values of Limit of Detection (LOD) and
45 into a 100 mL volumetric flask. Filter
Limit
paper was washed with the solvent and
calculated by using σ (standard deviation
volume was made up to mark. The
of response) and s (slope of the calibration
solution
with
curve) and by using equations, LOD =
methanol to get a concentration of 300
(3.3 x σ)/s and LOQ = (10 x σ)/s. To
μg/mL of ACBR and 15μg/mL of MTKT.
determine the robustness of the method,
The sample solution was then filtered and
the final experimental conditions were
20 μL of the test solution was injected and
intentionally altered and the results were
chromatogram was recorded for the same
examined by changing one factor at the
and the amounts of the drugs were
time. The parameters considered (±
calculated.
values) for the robustness study, flow rate
was
suitably
diluted
of
Quantitation
(LOQ)
were
(± 0.1 mL/min.) and pH (± 1) were Analytical Method Validation
studied.
The stability indicating RP-HPLC method was validated in terms of precision, accuracy,
specificity,
sensitivity,
robustness and linearity according to ICH guidelines. Method precision (inter-day and intraday) was determined using three concentrations and three replicates of each concentration.
Standard
solutions
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Degradation study of API and Tablet formulations ACBR and MTKT were subjected to various forced degradation conditions individually to effect partial degradation of the drug preferably in 10-20% range. The
forced
degradation
study
was
performed for the drug product ACBR and
102
MTKT bulk to determine whether any
exposed to same stress conditions and
observed degradation occurred because of
stress degraded samples were analysed by
drug properties or was due to drug
following above procedure described for
excipients
bulk analytes.
interactions.
Forced
degradation of the drug product was
RESULTS AND DISCUSSION
carried out under thermal, photolytic,
conditions. For photolytic stress, drug
Optimization of Chromatographic condition A well-defined symmetrical peak was
product in the solid state was exposed
obtained upon measuring the response of
with UV radiation. Minimum desired
eluent under the optimized conditions
exposure (200 Wh/m2) was observed after
after thorough experimental trials that can
irradiation for 24 h. Sample solution
be summarized. The mobile phase was
containing 2000 μg/mL of ACBR and 100
selected on the basis of best separation,
μg/mL were subjected to selected stressed
peak symmetry, theoretical plate etc. A
conditions. Samples except for photo
number of trials were taken for the
oxidation were protected from light. For
selection of mobile phase as mentioned
Acid and base degradation, solutions
here. Initially Methanol and Water were
containing ACBR and MTKT of the drug
tried in different ratios but result achieved
were prepared in 0.1N HCl and 1N NaOH
was not satisfactory. After that Methanol
analysed after 2 h exposure. Oxidative
and Acetoitrile as well as Acetonitrile and
degradation solution was prepared in
water were tried in different ratio and
water containing 3% v/v of H2O2 and
again result was found non-satisfactory.
analysed after 4 h. Sample for photolytic
Finally
studies were exposed UV radiations for 24
Acetonitrile and Methanol in the ratio of
h and were used. During dry heat study
60:40% v/v gave good separation and
samples were exposed to 800C for 24 h in
resolution. The effect of pH (adjusted with
oven and analysed. After exposure to
O-phosphoric acid) was studied initially at
desired
condition,
higher pH values and it shows baseline
samples were diluted with methanol to
disturbance and peak tailing. pH 3.2 was
achieve the nominal concentration of 300
found optimum after few of trial and
μg/mL of ACBR and 15 μg/mL of MTKT
errors. The effect of various flow rates on
which were based on their label strength
the formation and separation of peaks of
in
the analytes was studied and a flow rate,
acid/alkaline
and
stress
standard
containing
oxidative
degradation
solution.
ACBR and
stress
Formulation MTKT
were
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mobile
phase
consisting
of
0.8 ml/min was optimum with reasonable
103
time of analysis. UV detector response of
The linearity range for MTKT and ACBR
ACB was studied and the best wavelength
was found to be in the range of 5-25 μg/ml
was found to be 260 nm showing highest
and
sensitivity. Development studies revealed
Calibration data for MTKT and ACBR is
that methanol: acetonitrile (40:60 %v/v)
presented in table 1 and 2. Overlay
pH adjusted to 3.2 with O-phosphoric acid
Chromatogram of Std. API mixture of
at a flow rate of 0.8 ml/min was suitable
both
conditions
1.Calibration curve of both the drugs are
for
a
stability
indicating
100-500
the
drugs
μg/ml
is
respectively.
shown
in
fig.
method. ACBR was having retention time
shown in fig. 2 and 3.
3.45 min and MTKT was having retention
System Suitability Test (SST)
time 15.49 min. degraded products of
SST results are presented in Table 3.
ACBR and MTKT were well separated.
Chromatogram for system suitability is
Analytical Method Validation
shown in fig. 4.
The method was validated according to ICH guidelines. The following validation characteristics were addressed: linearity, range, accuracy, precision, sensitivity (LOQ
and
LOD)
and
robustness.
Specificity of the method was determined by analyzing solutions containing drug product, excipients and stress degraded samples.
All
chromatograms
were
examined to determine if ACBR and
Accuracy The data for accuracy for MTKT and ACBR are presented in table 4 and 5 respectively. The recovery range for MTKT and ACBR were found to be 99.49-100.81%
and
99.45-100.51%
respectively. Precision Repeatability
MTKT and its stress degraded product
The data for repeatability of MTKT and
coeluted with each other or with any
ACBR is depicted in table 6. The %RSD
excipient peak. Peak purity of stressed
was found to be 0.511% and 0.863% for
samples of ACBR and MTKT were
MTKT and ACBR respectively.
checked by using PDA detector. The purity angle within the purity threshold limit obtained in all stressed samples demonstrated
the
analyte
peak
homogeneity. Linearity, Range, LOD and LOQ
Intraday precision The data for intraday precision of MTKT and ACBR are presented in table 7. Range of %RSD was found to be 0.179-0.701% for MTKT and 0.142-0.586% for ACBR. Interday precision
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104
The data for interday precision of MTKT
the labelled amount of each component of
and ACBR are summarized in table 8.
tablet.
Range of %RSD was found to be 0.0770.391% for MTKT and 0.088-0.383% for
Stability Indicating Study Analytes and its stress
ACBR.
product were well separated. Although the
Robustness
conditions used for forced degradation
The data for robustness for MTKT and
were attenuated to achieve degradation in
ACBR
the
are
presented
in
table
9.
range
10–30%.
degradation
The
drug
was
Robustness of the method was evaluated
extensively degraded by acid hydrolysis,
by i) change in flow rate ii) change in pH.
alkaline hydrolysis, photolytic, Thermal
Assay of formulation Formulation was procured commercially from
the
market.
Formulation
was
and oxidative condition. Chromatograms of acid, alkali, oxidative, Photolytic and Thermal
degradation of ACBR
and
analyzed for simultaneous estimation of
MTKT in combined formulation are
MTKT and ACBR by the RP-HPLC
shown in Fig. 5 to 9, respectively. Stress
method. The assay values for MTKT and
conditions used and are presented in Table
ACBR are presented in Table 10. The
11 and 12. Chromatographic peak purity
result
data was obtained from the spectral
of
dosage
form
analysis
by
developed method was compatible with
analysis report
Figures and Tables Fig. 1 : Overlay chromatogram of Std. API mixture of MTKT and ACBR
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105
Fig. 2 : Calibration curve of MTKT
Fig. 3: Calibration curve of ACBR
Fig. 4: Chromatogram of Standard MTKT (5 μg/ml) and ACBR (100 μg/ml)
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106
Fig. 5 : Degradation peak of Standard API mixture of ACBR and MTKT in 0.1 M HCl after 2 hrs.
Fig. 6 : Degradation peak of Standard API mixture of ACBR and MTKT in 1M NaOH after 2 hrs
Fig. 7 : Degradation Peak of std. API mixture of ACBR and MTKT in 3%v/v H2O2 after 4 hrs.
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107
Fig. 8 : Degradation peak of std API mixture of ACBR and MTKT after 24 hrs of UV exposure
Fig 9 : Degradation peak of std API mixture of ACBR and MTKT after 24 hrs. in Hot air oven for 80oC
Table 1: Data of Linearity Area ± SD
Conc. in μg/ml Sr. No.
MTKT
ACBR
MTKT
ACBR
1
5
100
1109.784 ± 7.3970
1143.628 ± 3.6021
2
10
200
2331.780 ± 6.1427
2541.217 ± 5.0723
3
15
300
3445.345 ± 4.0549
3462.522 ± 5.8670
4
20
400
4715.748 ± 5.7981
4593.376 ± 6.9692
5
25
500
6016.050 ± 8.5052
5837.654 ± 6.4161
Correlation co-efficient
0.999
0.999
Slope
243.9
11.64
Intercept
135.2
16.66
Regression equation
243.9x - 135.2
11.64x - 16.66
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108
Table 2: Data of LOD and LOQ MTKT(μg/ml )
ACBR(μg/ml )
LOD
0.4807
1.412
LOQ
1.4570
4.281
Table 3 : Data of System suitability parameters Sr. No.
1 2 3 4 5 Average SD %RSD Retention time Theoretical plates Tailing Factor Resolution
Standard Response (mV*S) MTKT 1109.784 1118.458 1114.298 1102.259 1121.655 1113.262 1.8017 0.4871 16.49 5056 1.359
Std. Value
ACBR 1143.628 1151.912 1131.324 1147.584 1160.235 1146.935 1.1800 0.0590 3.450 10303 1.568 2.180
≤2% > 2000 Not more than 2 >2
Table 4 : Accuracy data of MTKT Conc. Conc. Spiked in added Total level sample in conc. (%) (μg/ml) (μg/ml) (μg/ml)
80%
10 10 10
8 8 8
18 18 18
100%
10 10 10
10 10 10
20 20 20
120%
10 10 10
12 12 12
22 22 22
Conc. Recovered
% Recovery
18.17 18.12 18.09 Avg. 20.16 20.19 20.14 Avg. 21.86 21.89 21.92 Avg.
100.94 100.67 100.50 100.70 100.80 100.95 100.70 100.81 99.35 99.50 99.64 99.49
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SD
%RSD
0.2218
0.2210
0.1258
0.1248
0.1450
0.1457
109
Table 5 : Accuracy data of ACBR Conc. Conc. Spiked in added Total level sample in conc. (%) (μg/ml (μg/ml) (μg/ml)
80%
100%
120%
Conc. Recovered
% Recovery
200
160
360
361.89
100.52
200
160
360
361.94
100.54
200
160
360
361.77 Avg.
100.49 100.51
200
200
400
397.51
99.38
200
200
400
398.13
99.53
200
200
400
397.85 Avg.
99.46 99.45
200
240
440
442.32
100.53
200
240
440
441.98
100.45
200
240
440
441.86 Avg.
100.42 100.46
SD
%RSD
0.0251
0.0250
0.0750
0.0755
0.0568
0.0566
Table 6 : Data of Repeatability study Peak area at 260 nm (mV*s) Sr No.
MTKT
ACBR
1
3445.345
3462.522
2
3421.257
3445.147
3
3455.236
3489.371
4
3425.347
3411.482
5
3467.589
3465.548
6
3440.951
3476.193
Mean
3442.620
3458.377
S.D.
17.59291
27.27936
% RSD
0.511
0.863
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110
Table 7 : Data of Intraday Precision Area Mean ± % SD (mV*s)
Conc. (μg/ml)
MTKT ACBR
%RSD
Area Mean ± % SD (mV*s)
MTKT
%RSD
ACBR
5
100
1110.835 ± 7.7917
0.7015
1147.62± 6.7337
0.5863
15
300
3495.249± 6.2657
0.1795
3505.40± 5.0075
0.1426
25
500
5962.317± 11.0949
0.1859
5803.62± 8.9770
0.1547
Avg.
0.3014
Avg.
0.2945
Table 8 : Data of Interday Precision Conc. (μg/ml)
Area Mean ± % SD (mV*s)
MTKT ACBR
%RSD
Area Mean ± % SD (mV*s)
MTKT
%RSD
ACBR
5
100
1112.546± 4.3711
0.3912
1145.32± 4.4734
0.3891
15
300
3497.478± 3.0412
0.08702
3508.12± 7.0500
0.2009
25
500
5959.987± 4.6282
0.07761
5801.99± 5.1117
0.0880
Avg.
0.1852
Avg.
0.226
Table 9: Data for Robustness study Robustness parameter
Drug
Rt(min.) ± SD
%RSD
MTKT
15.60 ± 0.0551
0.5314
ACBR
3.41 ± 0.0300
0.2327
MTKT
15.59 ± 0.0252
0.2561
ACBR
3.44 ± 0.0550
0.3097
MTKT
15.66 ± 0.0351
0.3349
ACBR
3.39 ± 0.0569
0.4397
MTKT
15.64 ± 0.0473
0.4835
ACBR
3.47 ± 0.0153
0.1276
0.9 ± 0.1ml/min.
Change in flow rate 1.0 ± 0.1ml/min.
3.5
Change in pH 4
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111
Table 10 : Data for Analysis of marketed formulation Amount taken (mg)
Average amount found (mg) ± SD
% Label claim ± SD
MTKT
15
14.88
99.23 ± 1.1229
ACBR
300
302.5
100.83 ± 0.2544
Table 11 : Data of Degradation study of MTKT Degradation condition
Time (hrs)
Area
Acidic/ 0.1 M HCl /2 hr./ Solution Alkaline/1.0 M NaOH/RT/ 2 hr/ Solution Peroxide/ 3% H2O2/4 hr/ Solution Photo/under UV ligtht / 24 hr/Solid
0
3449.22
14.92
99.46
2 0
415.94 3441.88
1.79 14.90
87.40 99.33
2
825.884
3.57
75.75
0
3446.75
14.93
99.53
2
654.74
2.83
80.72
0
3439.32
14.86
99.06
24
343.89
1.49
89.39
Thermal / 80°C/ 24 hr/ Solid
Conc. % % Assay (μg/ml) Degradation
Time (hrs)
Area
Acidic/ 0.1 M HCl /2 hr./ Solution
0
3468.54
301.23
100.41
2
471.64
39.16
86.35
Alkaline/1.0 M NaOH/RT/ 2 hr/ Solution Peroxide/ 3% H2O2/4 hr/ Solution Photo/under UV ligtht / 24 hr/Solid
0
3465.23
300.12
100.04
2
658.35
57.02
81.11
0
3470.15
300.21
100.07
2
728.70
63.04
78.34
0
3462.65
299.72
99.90
24
3482.12
29.97
88.35
0
3466.25
299.23
99.74
24
242.62
20.94
93.05
Thermal / 80°C/ 24 hr/ Solid
12.60
2.91
24.45
6.22
19.28
7.30
10.61
2.89
0 3440.02 14.88 99.20 3.60 24 123.84 0.54 96.40 Table 12 : Data of Degradation study of ACBR
Degradation condition
Conc. % Assay (μg/ml)
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Retention Time
6.78
% Degradation
Retention Time
13.65
14.98
18.89
13.95
21.66
14.09
11.65
6.96
6.95
13.92
112
CONCLUSION Stability-indicating RP-HPLC method for estimation of Montelukast sodium and Acebrophylline in their solid dosage form was established and validated as per the ICH guidelines. Different degradation products were found for drug substance and drug product in acidic, alkaline, oxidative,
thermal
and
photolytic
degradation. Peak of degraded products were not interfering with that of main drug. The developed method is simple, precise, accurate, specific, and robust. Hence it can be used for the routine analysis of Montelukast sodium and Acebrophylline.
Further
method
be
could
this
helpful
present for
the
identification of impurities through LCMS, degradation kinetic studies and establishment of probable degradation pathway. REFERENCES 1. Lipkowitz, M. A., & Navarra, T. (2001). The Encyclopedia of allergies. 2 (Eds.). facts on file inc. New York, p.279. 2. Tripathi, K. D. (2007). Essentials of medical pharmacology. 6(Eds.). Jaypee brothers medical publishers Ltd. Hyderabad. P.213-229. 3. Barar, F. S. K. (2006). Essentials of pharmacotherapeutics. 5 (Eds.). S. Chand and company Ltd. New Delhi.p.544-552. 4. Pozzi, E.(2007). Acebrophylline: An airway mucoregulator and anti-
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HOW TO CITE THIS ARTICLE
Thesia, D. U., Patel, B. P. (2014). Stability Indicating HPLC Method Development for Estimation of Montelukast Sodium and Acebrophylline in Combined Dosage Form Journal Club for Pharmaceutical Sciences (JCPS), 1(I), 99-114 © All Rights Reserved by “Journals Club & Co.”
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