Simultaneous Estimation of Ranitidine and Drotaverine in Combined Pharmaceutical Dosage Form by Derivative Spectrophotometric Method
Rajesh K. Patel1*, Ravi N. Patel1, Dr. Ashok L. Ganure1, Dr. Laxmanbhai J. Patel2
1Department of Pharma. Analysis, K.J. College of Pharmacy, Vadasma-382708,
2Department of Pharma. Analysis, Shree S.K. Patel College of Pharmaceutical Education and Research, Mehsana, Gujarat
*Corresponding Author E-mail: raj07181@gmail.com
ABSTRACT:
A Derivative Spectrophotometric method has been developed for simultaneous estimation of Ranitidine and Drotaverine in combined Pharmaceutical dosage forms. Methanol was used as solvent. The method involves the measurement of absorbance at two wavelength 322 nm (λmax for Ranitidine) and 306.5 nm (λmax for Drotaverine). The linearity lies between 5-60µg/ml for Ranitidine and 4-20µg/ml for Drotaverine. The accuracy and precision of methods were determined and validated statiscally. The method showed good reproducibility and recovered with %RSD less than 2.The method are found to be rapid, specific, precise and accurate and can be successfully applied for the routine analysis of simultaneous estimation of Ranitidine and Drotaverine in combined pharmaceutical dosage form.
KEYWORDS: Simultaneous, Derivative Spectrophotometric, Ranitidine, Drotaverine, %RSD
Ranitidine is white pale yellow crystalline powder, sensitive to light and moisture. Chemically it is 1, 1-ethenediamine-N-[2[[[5(dimethylamino)methyl]-2-furanyl]methyl] thio]ethyl]-N'-methyl-2-nitro monohydrochloride. It is used as H 2- receptor antagonist and is also used in the management of ulceration. It is official in IP1 and USP2. Drotaverine [(1 - (3, 4 – diethoxybenzylidene) - 6, 7 – diethoxy - 1, 2, 3, 4 tetrahydroisoquinoline) hydrochloride], a benzylisoquinoline derivative3 . It is a highly potent spasmolytic agent4. Literature survey revealed that various capillary electrophoresis5-6 and HPLC7-9 methods, have been reported for the determination of Ranitidine and Drotaverine, individually and combination with some other drugs. No Derivative spectrophotometric method for Simultaneous estimation of Ranitidine and Drotaverine in combined pharmaceutical dosage form has so far been reported. The review of literature prompted us to develop a precise simultaneous method for the estimation of Ranitidine and Drotaverine in combined dosage.
EXPERIMENTAL METHOD:
A double-beam UV-Visible spectrophotometer, model UV-1800 (Shimadzu, Japan) having two matched cells with 1-cm light path, was used to measure absorbance of the resulting solutions. Ranitidine (Lincoln pharmaceutical limited) and Dortaverine (Intas pharmaceutical limited) were produced from the market. Methanol was used as solvent.
Preparation standard stock solution (100μg/ml):
Accurately weighed 10 mg of Ranitidine and 10 mg of Drotaverine were transferred to two separate 100 ml volumetric flasks. 50 ml methanol was added to the flask. The drug was dissolved with sonication and the final volume was adjusted with methanol up to the mark to prepare 100μg/ml stock solutions of both drugs.
Preparation working standard solution:
Standard stock solution (100μg/ml) of Ranitidine and Drotaverine was used as working standard solutions.
ANALYSIS OF FORMULATION:
Preparation of sample solution:
Twenty tablets were weighed and powdered. Quantity of the powder equivalent to about 15 mg of Ranitidine and 4 mg of Drotaverine was transferred into 100 ml measuring flask and dissolved in methanol and sonicate for 20 minutes. The solution was filtered through Whatman filter paper No. 41 and the residues were washed thoroughly with methanol. The filtrate and washings were combined in a 100 ml volumetric flask and diluted to the mark with methanol to obtain final solutions of 150μg/ml of Ranitidine and 40μg/ml of Drotaverine.
Determination of wavelengths of maximum absorbance and wavelength of ZCP (Zero Crossing Point) for Ranitidine and Drotaverine:
The working standard solutions were scanned in the range of 200 nm to 400 nm against methanol as a blank. Maximum absorbance was obtained at 322 nm and 306.5 nm and the ZCP were found to be at 322 nm and 306.5 nm for Ranitidine and Drotaverine, respectively in Figure 1 and Figure 2.
Fig 1: First order spectra for Ranitidine
Fig 2: First order spectra for Drotaverine
METHOD OF VALIDATION:
Calibration curve (Linearity):
Accurately measured working standard solution of Ranitidine (0.5, 1.0, 2.0, 3.0 and 6.0 ml) and Drotaverine (1, 2, 3, 4 and 5 ml) was transferred to separate 10 ml volumetric flasks and diluted up to the mark with methanol. Absorbance was measured at ZCP of Ranitidine (322 nm) and ZCP of Drotaverine (306.5 nm) for Drotaverine and Ranitidine respectively using methanol as a blank. The calibration curve was constructed by plotting absorbance versus concentration corresponding to each working standard solutions. Each reading was average of three determinations. A calibration curve was plotted over a concentration range from 5-60μg/ml for Ranitidine and 4-20μg/ml for Drotaverine.
Accuracy and Precision:
The accuracy of the method was determined by calculating recoveries of Ranitidine and Drotaverine by the standard addition method. Known amounts of standard solutions of Ranitidine and Drotaverine (50, 100, and 150 % level) were added to previously analyzed sample solutions. The amount of Ranitidine and Drotaverine was analyzed by applying these values to the regression equation of the calibration curve. Precision was determined in terms of intra-day and inter-day precision.
Estimation of Ranitidine and Drotaverine in Formulation:
Test solution from tablets which contain Ranitidine (15.0, 30.0 and 45.0μg/ml) and Drotaverine (4.0, 8.0 and 12.0μg/ml) was transferred to separate 10 ml volumetric flasks and diluted up to the mark with methanol. Sample was measured at ZCP of Ranitidine (322 nm) and ZCP of Drotaverine (306.5 nm). Concentrations of both drugs were calculated from calibration curves which are shown in fig 1 and fig 2 respectively.
Recovery studies:
To study the accuracy of the proposed methods, recovery studies were carried out by standard addition method at three different levels. A known amount of drug added and percentage recoveries were calculated. The result of recovery studies were satisfactory table 1.
Table 1: Recovery studies of Ranitidine and Drotaverine
|
Drug |
Amount taken (μg/ml) |
Amount added (μg/ml) |
Amount found (μg/ml) ± S.D (n=3) |
% recovery ± S.D (n=3) |
|
Ranitidine |
10 |
5 |
14.71 ± 0.30 |
98.07 ± 2.00 |
|
10 |
10 |
19.6 ± 0.13 |
97.99 ± 0.67 |
|
|
10 |
15 |
25.07 ± 0.47 |
100.27±1.89 |
|
|
Drotaverine |
4 |
2 |
6.07 ± 0.05 |
101.13± .84 |
|
4 |
4 |
7.83 ± 0.13 |
97.93 ± 1.68 |
|
|
4 |
6 |
9.65 ± 0.12 |
96.46 ± 1.17 |
RESULT AND DISCUSSION:
Absorbance for Ranitidine and Drotaverine were recorded at 322 nm (ZCP of Ranitidine) and 306.5 nm (ZCP of Drotaverine). The developed method was validated as per ICH guideline, data for which are shown in the table 1 and table 2.The method was applied for the determination of both drugs in pharmaceutical dosage form and its result is given in table 3.
Table 2: Method validation parameters for Ranitidine and Drotaverine
|
Parameters |
Ranitidine |
Drotaverine |
|
Calibration range |
5-60μg/ml |
4-20μg/ml |
|
Detection limit |
1.08μg/ml |
0.57μg/ml |
|
Quantitation limit |
3.28μg/ml |
1.72μg/ml |
|
Slope |
0.0015 |
0.0003 |
|
Intercept |
0.0004 |
-0.00007 |
|
Mean |
99.55 |
100.09 |
|
Standard deviation |
1.92 |
1.43 |
|
% RSD |
1.92 |
1.43 |
|
Correlation coefficient |
0.9996 |
0.9978 |
|
Intraday RSD, % |
0.11-1.18 |
0-1.69 |
|
Interday RSD, % |
0.13-0.77 |
0-1.77 |
Table 3: Assay results of Ranitidine and Drotaverine
|
Brand |
Ranitidine |
Drotaverine |
||||
|
Amount taken (mg) |
Amount found (mg) ± S.D (n=3) |
Amount found (mg) ± S.D (n=3) |
Amount taken (mg) |
Amount found (mg) ± S.D (n=3) |
Amount found (mg) ± S.D (n=3) |
|
|
Brand I |
150 |
149.34 ±0.84 |
99.56 ±0.86 |
40 |
40.41 ± 0.65 |
101.03 ±0.63 |
|
Brand II |
150 |
149.67 ±0.91 |
99.78 ±0.93 |
40 |
39.47 ± 0.69 |
98.69 ± 0.72 |
CONCLUSION:
The method can analyse the drug in the presence of excipients and have specific nature. Detection and quantification limits describes the method is very sensitive. The method has linear response in the range of 5-60 μg/ml for Ranitidine and 4-20 μg/ml for Drotaverine. High % recovery and acceptable % CV values confirm established Derivative spectrophotometric method is accurate and precise. The analytical results demonstrate ability of developed Derivative spectrophotometric method to assay Ranitidine and Drotaverine in combined dosage form. Assay results found from the study show that the method is successfully applied for the analysis of Ranitidine and Drotaverine in combined dosage form.
REFERENCE:
1. Indian Pharmacopoeia, 1996; vol-2; 659.
2. United State Pharmacopoeia, National Formulary, USP 24, Asian Edition, 2000; 1462.
3. M.J. O’Neil.The Merck Index 13th edition; Merck and Co., Inc., New Jersey, 2001; 3489.
4. T.Olivier Finance and P. Aranyi Euro. J. Pharmacol., 2002, 449, 55-60.
5. Wu SM. Simultaneous determination of cimetidine famotidine nizatidine and ranitidine hydrochloride in tablets by capillary electrophoresis: Electrophoresis, 2001; 22:2758-62.
6. Wu SM. Head column field amplified sample stacking in capillary electrophoresis for determination of cimetidine famotidine nizatidine and ranitidine hydrochloride in plasma: Electrophoresis, 2001; 22:2717-22.
7. Lalla JK, Shah MU, Jain MB Sharma AH. Modified high-performance liquid chromatographic method for analysis of Drotaverine in human plasma. J. Pharm. Biomed. Anal. 11:1993:385-88.
8. Panigrahi D, Sharma R. Development and validation of an RP-HPLC method for simultaneous analysis of Drotaverine and Omeprazole in a tablet dosage form. Journal of Acta Chromatographica.20:2008:439-50.
9. Lunn G. HPLC Methods for Pharmaceutical Analysis. John Wiley and Sons, Inc., New York 2000.1073-89.
Received on 14.12.2011 Modified on 11.01.2012
Accepted on 15.01.2012 © AJRC All right reserved
Asian J. Research Chem. 5(2): February 2012; Page 215-217