International Journal of Drug Development and Research

Keywords

Famotidine, difference spectrophotometric method, 0.1 N HCl, 0.1 N NaOH

INTRODUCTION

Chemically, famotidine (FAM) (Figure 1) known as 3-([2-(diamino- methylene amino) thiazol-4-yl] methylthio)-N'-sulfamoylpropanimidamide is a histamine H2 receptor antagonist used in the treatment of peptic ulcer and gastro esophageal reflux disease [1,2].

Indian Pharmacopoeia [2], British Pharmacopoeia [3], European Pharmacopoeia [4] and United States Pharmacopoeia [5] described titrimetric method for the estimation of FAM in bulk form whereas, liquid chromatographic method was described for the assay of tablet, injection and oral suspension of FAM. Few methods have been described in the literature for the estimation of FAM as single formulation which include spectrophotometric [6-9], spectrofluorimetric [10, 11], HPLC [12-17], flow injection analysis [18], HPTLC [19]. Also numerous methods have been developed for the estimation of FAM in multicomponent formulation which includes spectrophotometric [20- 25], HPLC [26, 27], flow injection analysis [28] and HPTLC [29-31].

The selectivity and accuracy of spectrophotometric analysis of sample containing absorbing interference may be markedly improved by the technique of difference spectrophotometry[32]. The essential feature of difference spectrophotometric assay is that the measured value is the difference in absorbance (ΔA) between two equimolar solutions of the analyte in different chemical forms which exhibit different spectral characteristics [32].

No difference UV spectrophotometric method has been reported for estimation of famotidine. Therefore, an attempt has made to develop a simple, accurate, rapid and precise spectrophotometric method for the determination of famotidine in bulk and tablet dosage form.

MATERIALS AND METHOD

Chemicals and reagents

FAM was obtained as gift sample from Centurion Laboratories, Baroda, India. Analytical grade chemicals and distilled water were used during experimentation.

Instrument

A Shimadzu UV-1700 Pharma Spec UV-Visible spectrophotometer (UV probe 2.21 software) with a pair of 1.0 cm matched quartz cells was used for the measurement of absorbance.

Selection of solvent

About 0.1 M HCl and 0.1 M NaOH was selected as solvent to study spectral characteristics of FAM.

Preparation of standard solution

Stock solution of FAM (100 μg/ml) was prepared in 0.1 M HCl and 0.1 M NaOH separately. Appropriate volume of above stock solution was diluted up to 10.0 ml and the resulting solution (10 μg/ml) was used as working solution.

Preparation of sample solution

Twenty tablets of each brand of FAM (TOPCID® 40 tablet and FAMOTIN® 40 tablet) were weighed accurately and powdered finely. A quantity of tablet powder equivalent to 10 mg of FAM was accurately weighed and transferred into two separate 100 ml volumetric flask, 10 mL of 0.1 M HCl and 0.1 M NaOH was added in to respective flask and the content was ultrasonicated for 20 min. The volume was made up to the mark with same solvent and mixed well. The solution was further filtered using Whatman filter paper to remove any unwanted particulate matter. The filtered solution was further appropriately diluted with respective solvent to finally produce sample solution of concentration 10 μg/ml for analysis. The amount of FAM present in the sample solution was determined using the calibration curve of standard drug.

METHOD VALIDATION

The method was validated according to ICH Q2 (R1) guidelines for parameters like linearity, accuracy, precision, LOD, LOQ and specificity of the analyte [33]

Linearity

Aliquot portions of 0.5 – 3.0 ml of FAM stock solution was separately transferred into 10.0 ml volumetric flask. The volume was adjusted to the mark with 0.1M HCl and 0.1M NaOH so as to obtain a series of concentrations ranging from 5-30 μg/ml as reference and sample solution, respectively. The difference spectrum for famotidine was recorded by placing reference and sample solution of FAM in reference and sample cell, respectively. The difference in absorbance at wavelength between 290.60 nm (maxima) and 259 nm (minima) was calculated to find out the amplitude. Calibration curve was plotted by taking concentration of FAM (μg/ml) on X-axis and amplitude (ΔA) on Y-axis. The overlain difference UV absorption spectra of FAM (5 – 30 μg/ml) is shown in Figure 2.

Accuracy

The accuracy of the proposed method was determined by recovery study. The known amount of pure FAM was spiked to pre-analyzed tablet dosage form of FAM (TOPCID® 40 tablet and FAMOTIN® 40 tablet). Analysis of FAM was carried out at three concentration levels such as 80%, 100% and 120% within the specified linearity and range. The % recovery by proposed method was calculated using the formula as below.

The % recovery by proposed method was calculated using the formula as below.

Where,

E: Total amount of drug estimated (μg/ml)

T: Amount of drug taken from pre-analyzed

tablet dosage form (μg/ml)

P: Amount of pure drug added (μg/ml)

Precision

Precision was studied to find out intra and inter-day variations in the test method of FAM. The repeatability study (intra-day precision) was performed by analyzing the sample of FAM repeatedly within the day. The inter-day precision study was performed by analyzing the sample of FAM repeatedly at different days. Six determinations of working standard solution of FAM were performed. The results were expressed as % RSD.

Limit of detection (LOD) and limit of quantitation (LOQ)

LOD and LOQ of FAM by developed analytical method was calculated using the formula mentioned below.

Where,

σ: Standard deviation of the response

S: Slope of calibration curve

RESULT AND DISCUSSION

The aim of present work is to develop a simple, accurate, precise, reproducible and an economical difference UV spectrophotometric method to determine the amount of FAM present in pharmaceutical dosage form. The values were presented as amplitude (ΔA) of FAM in two different chemical forms exhibiting different spectral properties. The difference spectrum of FAM in 0.1M NaOH was recorded by taking 0.1M HCl solution as reference. The typical difference spectrum has shown characteristic maxima at 290.60 nm and minima at 259 nm.

Analysis of pharmaceutical dosage form

The assay result of TOPCID® 40 tablet and FAMOTIN® 40 tablet was found to be 99.09 ± 0.43 and 99.04 ± 0.94 respectively (Table 1).

Linearity

The proposed spectrophotometric method has shown linear relationship in the concentration range of 5 - 30 μg/ml (r2 = 0.9995) for FAM (Table 2, Figure 3).

Accuracy

The mean % recovery in TOPCID® 40 tablet and FAMOTIN® 40 tablet was found to be 99.17 ± 0.47 and 99.22 ± 0.59, respectively (Table 3).

Precision

The result of inter-day precision was expressed as % RSD and it was found to be 1.30. The result of intraday precision was expressed as % RSD and it was found to be 1.93. The % RSD value indicates the good precision of the method (Table 2).

Limit of detection (LOD) and limit of quantitation (LOQ)

The LOD and LOQ was found to be 0.4435 μg/ml and 1.3307 μg/ml for FAM (Table 2).

CONCLUSION

The result of the developed method for determination of FAM indicates that the method was accurate, precise and reproducible. The method is economical as compared to other reported analytical method. Hence this method can be used for routine analysis of commercially available formulation of FAM. The method is suitable for the determination of the FAM in tablet formulation without interference from commonly used excipients. The solvents used for the proposed method were inexpensive and simple to prepare. The method could be used in a quality control laboratory for routine drug analysis.

ACKNOWLEDGEMENT

We are thankful to Centurion Laboratories, Baroda (India) for providing gift sample of FAM for research purpose. We would also like to extend thanks to Dr. S. B. Bari Sir, Principal, H. R. Patel Institute of Pharmaceutical Education and Research, Shirpur for providing research facilities to carry out this project work.

Tables at a glance

Table 1 Table 2

Figures at a glance

Figure 1 Figure 2

References

1. Tripathi, K. D., 2003. Essentials of Medical Pharmacology, 5thed. New Delhi: Jaypee Brothers Medical Publishers, p. 588.
2. British Pharmacopoeia, Her Majesty's Stationary Office, London, 2009, p. 767.
3. United States Pharmacopoeia, U.S.P.Convention, XXIV Rockville, 2009, p. 1865.
4. Darwish, I. A.; Hussein, S. A.; Mohmoud A. M.; Hassan A. I., Sensitive indirect spectrophotometric method for
5. determination of H2-receptor antagonists in pharmaceutical formulations, Int. J. Biomed. Sci. 2007, 3(2), 123-103.
6. Rahman, N.; Kashif, M., Application of ninhydrin to spectrophtometric determination of famotidine in drug formulation, IL Farmaco 2003, 58(10), 1045- 1050.
7. Ayad, M. M.; Shalaby, A.; Abdellatef, H. E.; Hosny, M. M., New colorimetric methods for the determination of TrazodoneHCl, Famotidine and DiltiazemHCl in their pharmaceutical dosage forms, Anal. Boianal. Chem. 2003, 376(5), 710-714.
8. Okram, Z. D.; Kanakapura, B.; Pavagada, J. R.; Kanakapura, B. V., Simple and sensitive UV spectrophotometric methods for determination of famotidine in tablet formulations, Farmacia 2011, 59(5), 647-657.
9. Walash, M. I.; El-Brashy A.; El-Enany N.; Wahba M. E. K., Spectrofluorimetric determination of famotidine in pharmaceutical preparations and biological fluids through ternary complex formation with some lanthanide ions: application to stability studies, Int. J. Biomed. Sci. 2009, 5(2), 158-168.
10. El-Bayoumi, A. A, El-Shanawany, M. E. El-Sadek and A. Abd El-Sattar, Synchronous spectrofluorimetric determination of famotidine, fluconazole and ketoconazole in bulk powder and in pharmaceutical dosage forms, Spectrosc.Lett., 1997, 30, 25-46.
11. Dowling, G.; Gallo, P.; Fabbrocino, S.; Serpe, L.; Regan, L., Determination of famotidine in human plasma and urine by high-performance liquid chromatography, Food Addit. Conta. 2008, 25(12), 1497-1508.
12. Zendelovska, D.; Stafilov, T., High-performance liquid chromatographic determination of famotidine in human plasma using solid-phase column extraction, J. Serb. Chem. Soc. 2003, 68(11), 883-892.
13. Zarghi, A.; Shapaati, A.; Foroutan, S. M.; Khoddam, A., Development of a rapid HPLC method for determination of famotidine in human plasma using a monolithic column, J. Pharm. Biomed. Anal. 2005, 39(3-4), 677-680.
14. M.Vamsi Krishna; G. Madhavi; L. A. Rama Prasad; D. GowriSankar, Impurity profiling of famotidine in bulk drugs and pharmaceutical formulations by RP-HPLC method using ion pairing agent, Der Pharm. Lett., 2010, 2(3), 1-11.
15. Helali, N.; Darghouth, F.; Monser, L., RP-HPLC determination of famotidine and its potential impurities in pharmaceuticals, Chromatographia 2004, 60(7, 8), 455-460.
16. Biffar, S. E.; Mazzo, D. J., Reversed-phase determination of famotidine, potential degradates, and preservatives in pharmaceutical formulations by high-performance liquid chromatography using silica as a stationary phase, J. Chromatogr. 1986, 363(2), 243-249.
17. Tzanavaras, P. D.; Verdoukas A.; Balloma, T., Optimization and validation of a dissolution test for famotidine tablets using flow injection analysis, J. Pharm. Biomed. Anal. 2006, 41(2), 437-441.
18. Singh, S.; Kumar, S.; Sharda, N.; Chakrabarti A. K., New findings on degradation of famotidine under basic conditions: identification of a hitherto unknown degradation product and the condition for obtaining the propionamide intermediate in pure form, J. Pharm. sci. 2002, 91(1), 253-257.
19. Nyola N.; Govinda S. J.; Kumavat M.; Kalra N.; Singh G., Simultaneous estimation of famotidine and ibuprofen in pure and pharmaceutical dosage form by UV-Vis spectroscopy, Int. Res. J. Pharm., 2012, 3(4), 277-280.
20. Tajane D. D.; Gite S. R.; Shah A. R.; Kale A. B.; Gadhave R. V.; Choudhari V. P., Spectrophotometric simultaneous determination of famotidine and domperidone in combined tablet dosage form by ratio derivative and area under curve method. Der Pharm. Sin., 2011, 2(3), 60-66.
21. Patel D. P.; Shah R. R.; Patel A. P.; Tank P. K., Development and validation of first order derivative uv-spectroscopic method for estimation ofibuprofen and famotidine in synthetic mixture, Pharma Science Monitor, 2012, 2506-2515.
22. Singhvi I.; Prajapati A., Development and validation of analytical methods for simultaneous estimation of ibuprofen and famotidine in bulk and tablets using UV-Visible spectroscopy, Inventi Rapid: Pharm Analysis & Quality Assurance, 2012, 12, 19.
23. Shah D. A.; Suthar D. J.; Nagda C. D.; Chhalotiya U. K.; Bhatta K. P., Estimation of ibuprofen and famotidine in tablets by second order derivative spectrophotometery method, Arabian J. Chem., 2012, XXX, XXX-XXX, 1-4.
24. Kesur B. R.; Salunkhe V. R.; Magdum C. S., Development and validation of UV spectrophotometric method for simultaneous estimation of ibuprofen and famotidine in bulk and formulated tablet dosage form, Int J Pharm PharmSci, 2012, 4(4), 271-274.
25. Nyola N.; Jeyabalan S. N., Simultaneous estimation of ibuprofen and famotidine in pure and combination dosage form by RP-HPLC, Journal of Applied Pharmaceutial Science, 2012, 2(5), 79-83.
26. Shah D. A.; Suthar D. J.; Baldania S. L.; Chhalotiya U. K.; Bhatta K. P., Development and validation of liquid chromatographicmethod for estimation of ibuprofen and famotidine in combined dosage form, Analytical Chemistry, 2012, 2012.
27. Kamath B. V.; Shivram K.; Shah A. C., Determination of diclofenac sodium, famotidine and ketorolac tromethamine by flow injection analysis using dichloronitrophenol, J. Pharm. Biomed. Anal., 1994, 12(3), 343-346.
28. Dubey N.; Jain D. K.; Jadhawani S., Stability indicating HPTLC method for simultaneous estimation of famotidine, paracetamol and ibuprofen in combined tablet dosage form, J. Planar Chromatogr.--Mod. TLC, 2012, 25(2), 162.
29. Sathiyanarayanan, L.; Kulkarni, P. V.; Nikam, A. R.; Mahadik, K. R., Rapid densitometric method for simultaneous analysis of famotidine and domperidone in commercial formulations using HPTLC, Der Pharm. Sin., 2011, 3(1), 134-143.
30. Pawar S. M.; Patil B. S.; Patil R. Y., Validated HPTLC method for simultaneous quantitation of famotidine and domperidone in bulk and formulation, Int. J. Adv. Pharm. Sci., 2010, 1, 54-59.
31. Beckett, A. H., Stenlake, J. B., 1997. Practical pharmaceutical chemistry, 4thed. New Delhi: CBS publishers and distributors. p. 281.
32. ICH Validation of analytical procedures: Text and methodology Q2 (R1), 2005.