INTRODUCTION:

A drug, is any substance that, when absorbed into the body of a living organism, alters normal bodily function.In pharmacology, a drug is "a chemical substance used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being. Naproxen sodium is a non-steroidal anti-inflammatory drug used to relieve moderate to severe aches and pains ^1-3. The chemical name is (S)-6-methoxy-α-methyl-2-napthalene acetic acid, sodium salt or sodium (2S)-2-(6-methoxy-2-nephthyl)-propanoate. The structure of naproxen sodium is shown in fig 1. Its molecular weight is 252.24. It is an odorless, white off-white, hygroscopic crystalline solid, which is freely soluble in water and methanol. Most of its therapeutic activity is probably mediated through prostaglandin synthesis inhibition. Once dissolved in biologic fluids, Naproxen sodium is chemically identical species and has the same biologic properties. Naproxen sodium salt is more rapidly absorbed than Naproxen and used for rapid analgesia. Administration of Naproxen as the sodium salt however permits more rapid absorption from the gastrointestinal tract peak plasma concentration is reached in 1 or 2 hours after ingestion of the sodium salt. Food reduces the rate but not the extent of absorption ⁴. Most often the Naproxen Sodium is marketed as S-Enantiomer. Naproxen sodium is sold under a variety of different brand names, including Aleve, Anaprox, Naprelan etc.

Naproxen sodium has one Chiral center and hence exists as two Enantiomers. Naproxen sodium has always been marketed as the single active Enantiomer.

Islam Ullah Khan⁵reported a method for spectrophotometric determination of Naproxen in pure and pharmaceutical preparations. Naproxen reacts with 1-naphthylamine and sodium nitrite to give an orange red. Color having maximum absorbance at 460-480 nm. Several chromatographic methods have been reported for determination of Naproxen sodium in raw materials⁶ and intestinal perfusion samples⁷. These methods used for analysis of the related compound have been applied in the different. Chromatographic conditions have various mobile phases, columns and detector systems. Therefore some of the above methods have not only adequate retention⁶, but also have not been formally validated⁸. On the other hand although the retention time of Naproxen sodium is shorter than 2 min in the HPLC method reported by Monser et.al., the column used in that study is not easily commercially available⁹. Biological fluids can be analysed for Naproxen. Using HPLC^10-12. Gas liquid chromatography¹³, Fluorimetry¹⁴, UV Spectrophotometry¹⁵ and Mass fragmentography¹⁶.

Although phosphorimetry is sensitive and mole selective than flurimetry for the analysis of various other compounds. Only one phosphorimetric method has been proposed for this compound in micellar medium¹⁷. Naproxen sodium with other compounds in the samples was determined by using HPLC³⁷, chemo metric methods^18,19 and capillary electrophoresis²⁰.

Fig1: Structure of Naproxen Sodium

The P^H solubility profile of Naproxen sodium was obtained in the P^H range 1.2 to 7.4 by determining the solubility of the drug in different media. Anti-inflammatory effects of Naproxen are generally thought to be related to its inhibition of cycle-oxygenase and consequent decreases in prostaglandin concentrations in various fluids and tissues ²¹. The extensive use of Naproxen formulations requires the development of a rapid, selective and accurate method that can be used in routine quality control. Naproxen in commercial formulation has been determined by coulometry^22,23, oscillometric titration²⁴, first and second derivative UV spectrophotometry and high performance liquid chromatography²⁵. The unit status pharmocopeia XX1-1985²⁶ and the Real Farmacopea Espanola – 1997²⁷ describes a UV spectrophotometric method. Chilukuri S. P. Sastry²⁸ reported a method for spectrophotometric determination of some analyzed and anti-inflammatory agents with 3-methyl 2-benzothiazolinone hydrazone hydrochloride.

ULKU Dilek Uysal²⁹ described a method for the determination of Naproxen Sodium through potentiometry. A solvent system consisting of aqueous solution of 20% ethanol (V/V) at anionic strength of 0.1 adding sodium chloride was found to be suitable for the determination of Naproxen. Same solvent, solvent system was employed for titrant of 0.1 N Hydrochloric acids and to titrate the active material.

R.K. Maheshwari³⁰ reported a method for quantitative estimation of Naproxen in tablets using ibuprofen sodium as hydrotropic agent. 0.5M ibuprofen sodium solution has been used as hydrotropic solubiliging agent for naproxen, a poorly water soluble drug and in it there was more than 350 fold enhancement in the solubility solution was employed to extract out the drug from its tablet dosage form for quantitative estimation by titrimetry.

Bassam M. Tashtoush³¹ described a sensitive, rapid method using an isocratic high-pressure liquid chromatography and fluorometric detection for the determination of Naproxen sodium in plasma. Reverse phase micobondapack column was used with a mobile phase consisting of 42% acetonitrile and 58% water adjusted to pH 3 using phosphoric acid. The fluorometric detector with an excitation wavelength of 270 nm and emission wavelength of 340 nm provided high sensitivity and no interferences from plasma constituents.

Hiraietal³² reported a detection method for Naproxen sodium in plasma sample. It requires extraction and separation sample preparations of HPCL methods were tedious. Usually it involves extraction, separation and then detection of Naproxen in plasma. GLC method required a minimum plasma sample of 0.5ml several HPLC methods were reported using UV detectors³³

Erdal Dinc³⁴ described a method for chemometric determination of naproxen sodium and pseudoephedrine hydrochloride in tablets by high performance liquid chromatography the combination of naproxen sodium and pseudoephedrine Hydrochloride has an effect as a pain reliever, fever reducer and nasal decongestant in pharmaceutical tablet formulations. Particularly the above combination temporarily relieves cold, sinus and flu symptoms such as sinus pressure, minor body aches and pains and headache.

Bustamante P.³⁵ described the expanded Hansen method for determination of the solubility parameters of two non-steroidal. Anti-inflammatory drugs, naproxen and sodium diclofenac. The solubility of both drugs was measured in pure solvents of several chemical classes and the activity co-efficient was obtained from the molar heat and the temperature of fusion. Differential scanning calorimetry was performed on the original powder and on the solid phase after equilibration with the pure solvents, enabling detection of possible changes of the thermal properties of the solid. Phase that might change the value of the activity. Coefficient the molar heat and temperature of fusion of sodium diclofenac could not be determined because this drug decomposed near the fusion temperature. The best results for both drugs were obtained.

Abdel-Aziz M. Wahbi³⁶ reported simultaneous determination of the two non-steroidal Anti-inflammatory, drugs; Napoxen and Diflunissal by chemo metric spectrophotometry and high performance liquid chromatography.

The other simultaneous methods reported are Bebawy and El-Kousy³⁷ and Perez-Ruiz et.al Abdel³⁸ reported chemometric spectrophotometric and High performance liquid chromatograph methods have been developed for the simultaneous determination in their synthetic mixtures and their tables. The studied chemometric spectrophotometric methods are multivariate methods including classical least squares, principal component reglesson and partial least squares and the second derivative of the ration spectra method. Several analytical methods have been published for the determination of Naproxen sodium in pharmaceutical preparations and biological fluids. These methods included first derivative a non-linear variable-angle synchronous fluorescence spectroscopy³⁹ capillary isotachophoresis⁴⁰and flow-injection analysis⁴¹. Therefore the author described a simple, reliable, sensitive and less time consuming method for the determination of naproxen sodium.

MATERIALS AND METHODS:

A Jasco (Model Uvidec-610 UV-VIS Spectrophotometry with 1cm matched quartz cuvettes was used for all absorbance measurements.

Standard Naproxen Sodium and its commercial Tablet Apranax ® Labeled 550 mg respectively were purchased from Merck.

Bromocresol green solution and bromothymol blue , 0.04% alcoholic ⁴²

Preparation of Solutions:

Stock Solution: - Stock solutions were prepared by dissolving 5mg of Naproxen sodium and 50ml of water.

All other chemicals were of analytical glade and provided from Merck.

Procedure:

An aliquot of the Naproxen sodium stock solution and 0.1 ml Bromocresol green were introduced into a 10ml standard flask and made up to volume with water. The resulting absorbance of the blue color was measured at 616nm employing all reagents. A similar procedure was adopted for Bromothymol blue and the resulting absorbance was measured at 598nm. The experiments were repeated with different volumes of standard Naproxen Sodium solution and a calibration curves were prepared the color reaction obeys Beer’s law in both the cases from 0.01 to 5mg/10ml of Naproxen sodium.

RESULTS AND DISCUSSION:

Spectral characteristics:

The absorption spectra of the reaction product of Naproxen sodium with bromocresol green shown in fig 2and3 with maximum absorption λ _max616nm and 598nm in the case of bromothymol blue respectively. The blank solution was slightly yellowish in color that had negligible absorbance at the λ _max in which the drug is determined. The thus formed color was stable for more than three hours. A temperature range of 20-30ºC is selected for the reaction. Beer’s law was obeyed and the linearity graph is shown in fig 4 in the concentration range of 0-01-5mg/10ml of Naproxen sodium.

Fig 2: Spectrophometric determination of naproxen sodium with bromocresol green

Fig:3 Spectrophotometric determination of naproxen sodium with bromothymol blue

Effect of color producing reagent:

The rate of formation of complex in solution is generally rapid (45 seconds in color reaction) changes in spectrum or color are associated with a transfer/interchange of electrons when such molecules. Under go properly oriented collisions. Thus Naproxen sodium acts as an efficient electron donor. The absorbance of the developed color was stable for more than three hours.

Sensitivity:

The results for the determination of Naproxen sodium are shown in tables 1and2 which reveal the sensitivity, validity and repeatability of the method. The method is also reasonably precise and accurate, as the amount taken from various samples is known and the amount found by the above procedure does not exceed the relative standard derivative of 0.74%. The optimization has been done at lower analyte concentration.

Table1: Determination of naproxen sodium

Naproxen Sodium taken (mg)/10ml	Naproxen Sodium found (mg)/10ml	Relative Standard deviation %
0.1	0.134	0.74
0.2	0.190	0.52
0.4	0.395	0.25
1.5	1.493	0.07
2.0	2.010	0.05
2.5	2.5	0.04

Table: 2 Optical characters, precision and accuracy

Parameter	Values
Max (nm)	616
Relative standard deviation (RSD)%	0.74%
% range of error (confideny limit) at 95% confidence level	10 +-0.025

CONCLUSION:

The spectrophotometric method for the determination of Naproxen sodium is simple, reliable, sensitive and less time consuming. The color reaction is selective for Naproxen sodium. The advantage of the present procedure is that it does not require many solvents, where as the HPCL procedures are long, tedious and expensive, involving many reagents and solvents showing high RSD value.

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Received on 06.01.2011 Modified on 01.03.2011

Asian J. Research Chem. 4(5): May, 2011; Page 715-718