Development and Validation of new analytical methods for the estimation of Naproxen Sodium

1. DEVELOPMENT AND VALIDATION OF NEW ANALYTICAL
METHODS FOR THE ESTIMATION OF SELECTED
DRUG IN PHARMACEUTICAL DOSAGE FORM
Department of Pharmaceutical Analysis & Quality Assurance,
Roland Institute of Pharmaceutical Sciences,Berhampur-10.
SABYA SACHI DAS
M.PHARMA(PHARMACEUTICS)
ROLAND INSTITUTE OF PHARMACEUTICAL SCIENCES,
BERHAMPUR,ORISSA

2. Table-8:Naproxen sodium in Methanol :
TBAHS(80:20)
Concentration
(μg/ml)
Retention
Time
Peak Area Flow Rate
30 4.512 7713785 1.2ml/min
Fig5.

3. Preparation of Mobile Phase
0.01M TBAHS was prepared by dissolving 3.3954gm of TBAHS
salt in 1000ml tripple distilled Water. The prepared solution was
ultrasonicated for 30 minutes and was filtered through a 0.45µ
membrane filter. Methanol of HPLC grade was also ultrasonicated
for 30 minutes and filtered through a 0.45µ membrane filter.
Preparation of Stock Solution of Drug
10mg
Drug
1000μg/
ml
Stock
Solution
Dissolved in 10ml of Methanol

4. Table-9:Optimized Chromatographic Conditions
Parameters Method
Column (Stationary phase)
Enable C-18 G(250 x 4.6 mm, packed with 5μ)
column
Mobile Phase Methanol:10mM TBAHS(80:20, v/v)
Flow rate (ml/min) 1.2
Column back Pressure(kgf/cm2)
(kgf/cm2)
167
Run time (min) 6
Column temperature (°C) Ambient
Volume of injection loop (l) 20
Detection wavelength (nm) 231
Drug RT(min.) 4.512

5. Table-10:Linearity Range of Naproxen sodium
Concentration
(µg/ml)
Peak Area
0.01 25438
0.05 38248
0.1 62742
0.5 129288
1.0 282503
1.5 440838
2.0 609460
5.0 1585995
10 2597476
20 4934534
30 7713785
40 9828388
60 14567294

6. Calibration Curve of Naproxen sodium by
RP-UFLC Method
y = 243851x + 94446
R² = 0.9991
0
2000000
4000000
6000000
8000000
10000000
12000000
14000000
16000000
0 10 20 30 40 50 60
PeakArea
Concentration(µg/ml)
Calibration Curve of Naproxen sodium by
RP-UFLC Method
Fig6.Calibration curve of Naproxen sodium by RP-UFLC method.

7. Table -11:Retention Times of the Pure drug and Formulation
Sl. No. Name of the
Peaks
Pure drug Formulation
Retention
Time (min.s)
Retention
Time
(min.s)
1. Naproxen 4.512 4.553

8. Analysis of Commercial Formulation
20 Tablets
Powder10mg Of
drug
was
taken in a
10 ml Vol. Flask
Filtered through 0.45µ
membrane filterInjected in to
UFLC
Weighed & Powdered
Sonicated for 30 mins
From this Test Dilutions
were prepared

9. Table-12:Analysis of Commercial Formulation
Formulation Labeled
Amount (mg)
Observed
Amount*mg
±S.D.
% Recovery*
by proposed
method ±S.D.
%RSD
Naprosyn Tablet 500 498.6
±1.7959
99.71
±0.0.36
0.362
*Average of three determinations

10. Concentration(μg/ml) Peak Area *±S.D.;%
R.S.D.
10 2553301.83  29484.22;1.2
Concentrati
on
(µg/ml)
Intraday
Peak
Area*±S.D
%R.S.D Interday
Peak Area
*±S.D
%R.S.
D
10 2550157 
18173.06
0.71 2547373.16
 19698.05
0.77
*Average of six determination
Table- 12.1Instrument Precision
Table-13:Precision
Table- 12.2Method Precision

11. Table-14:Accuracy
Sample
ID
Concentration
(g/ml)
%Recovery
of
Pure drug
Statistical
Analysis
P* F**
99.93
Mean=100.01%
S.D.=0.0784
%RSD=0.078
S1:80% 16 20
S2:80% 16 20 100
S3:80% 16 20 100.12
S4:100%
20 20
100.1
Mean=99.66%
S.D.=0.8339
%RSD=0.84S5:100%
20 20
98.5
S6:100%
20 20
100.4
S7:120%
24 20
100.79
Mean=99.93%
S.D.=0.863
%RSD=0.86S8:120%
24 20
98.75
S9:120%
24 20
100.25

12. Table16: System Suitability Parameters
Parameters
Obtained Values
Retention
Time(min)
4.512
Theoretical
plates (N)
6274
Correlation
coefficient(
R)
0.9991
Tailing factor (T) 1.442
LOD (g/ml) 0.005
LOQ (g/ml) 0.01

13. Forced Degradation Studies
Forced Degradation studies were carried out to
evaluate the stability of the drug in different stress
conditions like Acid Degradation, Alkaline
Degradation, Oxidative Degradation, Photolysis
,Elevated Temperature & Bench Top Stability. This
study also helped in determining the specificity of the
proposed method in presence of degradation products.

14. Acidic Degradation
Fig7.Representative Chromatogram of Naproxen sodium(30g/ml)
untreated drugs.
Fig8.Representative Chromatogram of Naproxen sodium(30g/ml)
acid degraded drugs.

15. Fig9.Representative Chromatogram of Naproxen sodium(30g/ml)
Alkaline treated drugs
Fig 10. Representative Chromatogram of Naproxen sodium (30g/ml) pure oxidised
drug.

16. Table-18: Robustness
Result for Robustness study
Parameters RT(min) Theoretical
Plates
TailingFactor
TBAHS(mM)
9.5 4.464 5536 1.326
10 4.588 6275 1.428
10.5 4.498 6550 1.239
Methanol(%)
78 5.029 7143 1.135
80 4.588 6275 1.428
82 4.217 5480 1.488
Wavelength(nm)
226 4.588 6345 1.428
231 4.588 6275 1.428
236 4.588 6273 1.428

17. Results and discussion
From the linearity it was found that the drugs Naproxen sodium obey
linearity within the concentration range of 0.01-60g/ml. From the
results shown in precision it was found that % RSD is less than 2%;
which indicates that the proposed method has good reproducibility.
From the results shown in accuracy it was found that the percentage
recovery values of pure drug from the pre-analyzed solutions of
formulations were in between 100.11%-100.52%, which indicates that
the method was accurate and also reveals that the commonly used
excipients and additives present in the pharmaceutical formulations
were not interfering in the proposed method .
The forced degradation study revelaed that in the applied stress
conditions the drug Naproxen sodium was more susceptible to
degradation. In acid, alkali and photolytic degradation conditions the
drug degraded to a very high extent than compared to other stress
conditions applied. The system suitability parameters also reveal that
the values were within the specified limits for the proposed method.

18. CONCLUSION
All the proposed methods are simple, selective, reproducible, sensitive
and accurate with good precision. Some of the methods were proved to
be superior to most of the reported methods. All these proposed
methods for estimation of selected drug such as Naproxen sodium was
successfully applied either in bulk or pharmaceutical formulations.
The proposed methods can be used as alternative
methods to the reported ones for the routine determination of selected
drugs under the study in bulk and pharmaceutical dosage forms.
Thus the purpose of the present investigation was
successfully achieved

19. References
•http://en.wikipedia.org/wiki/ Naproxen sodium
•http://www.medlineindia.com/Naproxen sodium
•Asian Journal of Pharmaceutical & Clinical Research; Apr2011, Vol. 4
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