Novel Spectrophotometric Estimation of Naproxen Tablet Formulations Using Sodium Citrate as Hydrotropic Solubilizing Agent

Pani Kumar A.D.*, Sunitha G., Venkat Raju Y., Rama Krishna K., Swathi B., Praveen CH. and Swetha Mora

Department of Pharmaceutical Analysis and Quality Assurance, Gokaraju Rangaraju College of Pharmacy, Hyderabad, Andhra Pradesh, India.

*Corresponding Author E-mail: panindrapharma@yahoo.co.in

ABSTRACT:

Hydrotropy is one of the solubilizing techniques to enhance the solubility of poorly water soluble drugs. In the present investigation, hydrotropic solution of sodium citrate (0.1M) was employed as solubilizing agent to solubilize the poorly water soluble drug Naproxen fine powder and its tablet dosage form for spectrophotometric determination in UV region. Naproxen shows maximum absorbance at 330 nm and follows Beer’s law in concentration range of 20-140 mcg/mL. Results of analysis were statistically validated for the linearity, precision, LOD, and LOQ. The proposed method is new, simple, accurate, reliable, more economic and can be successfully employed in routine to analyze Naproxen tablets. Either hydrotropic agent or commonly used tablet additives did not interference in analysis. The percentage recovery was within the range between 99 and 100.

KEYWORDS: Sodium citrate, Naproxen, Spectrophotometric.

INTRODUCTION:

Hydrotropy is one of the solubilizing techniques to enhance the solubility of poorly water soluble drugs.¹ Naproxen is chemically (2S)-2-(6-Methoxynaphthalen-2-yl) propanoic acid. It is white or almost white, crystalline powder. It is practically insoluble in water, soluble in ethanol (96 per cent) and in methanol. Structure of Naproxen is shown in figure – I.

Here calibration curve method was employed by using hydrotropic agent for the estimation of Naproxen in pure and tablet dosage forms. “Hydrotropic agents are concentrated aqueous solutions which are used to increase the aqueous solubility of another solute (poorly water soluble drug)”^2-5.

In the present investigation, hydrotropic solublizing agent, 0.1 M Sodium citrate was employed to solubilize Naproxen fine powder and its tablet dosage form to carryout spectrophotometric analysis. UV spectrum of Naproxen in sodium citrate (hydrotropy) shown in figure-II.

MATERIALS AND METHODS:

Shimadzu UV-Visible spectrophotometer (Model UV-1800) with 1cm matched quartz cells was used for spectrophotometric analysis. Naproxen bulk drug sample was obtained as gift sample from Divi’s Laboratories Ltd. (India). The tablets of Naproxen were procured from the local market. All other chemicals and solvents used were of analytical grade.

Experimental Methods:

Calibration curve:

The standard stock solution (100mcg/mL) of Naproxen was prepared by solubilizing, accurately weighed 100 mg Naproxen in 100 mL 0.1 M sodium citrate. The stock solution was further diluted with distilled water to obtain various dilutions. Standard dilutions of 20, 40, 60, 80, 100, 120 and 140 mcg/mL of drug were used to plot the calibration curve by taking the absorbance at 330 nm using distilled water as blank. The Beer’s–Lambert law was observed in the concentration range 20-140 mcg/mL for naproxen as shown in Fig-III. Calibration curve for naproxen is shown in figure-IV. The linearity table is shown in Table-I. The linearity of calibration graph was validated by high value of correlation co-efficient (r²) = 0.999 and linear regression equation Y=0.007X + 0.0089.

Figure – I: Structure of Naproxen

Figure II: UV spectrum of Naproxen in sodium citrate

A indicates 0.1M Sodium citrate in water,

B indicates spectrum of Naproxen in 0.1M sodium citrate diluted with distilled water (10mcg/ml),

C spectrum of Naproxen in methanol dilution with distilled water (10mcg/ml).

Figure –III: Beer’s–Lambert law range (20-140 mcg/mL) for naproxen

Preliminary solubility studies:

Determination of solubility studies of Naproxen in 0.1 M sodium citrate and distilled water was carried out at 25° C. Saturated amount of drug was added to volumetric flasks containing hydrotropic solution and distilled water. Volumetric flasks were shaken mechanically for 24 hrs at 25° C, 100 rpm in orbital shaker. These solutions were allowed to equilibrate for the next 24hrs and filtered through 0.45 micron whattmann filter paper. Filtrate were diluted with distilled water and analyzed spectrophotometrically to determine the solubilities. The enhancement in solubility of Naproxen in hydrotropic solution was found to be more than 40 folds as compared to distilled water.

Table I: Linearity

Concentration (mcg/ml)	Absorbance ± SD
0	0
20	0.170 ± 0.001
40	0.282 ± 0.001
60	0.422 ± 0.001
80	0.560 ± 0.001
100	0.717 ± 0.001
120	0.845 ± 0.001
140	0.990 ± 0.001

Figure - IV: Calibration curve of Naproxen in sodium citrate

Analysis of Naproxen tablets using 0.1M Sodium citrate:

20 tablets (Naprosyn, Naproxen tablets I.P. 250mg & 500mg) were weighed and grounded to fine powder. Powder equivalent to 200 mg of Naproxen active ingredient was solubilized in 200 ml of 0.1 M sodium citrate solution, sonicate for 20 minutes. The solution was filtered through whatmann filter paper. Filtrate was appropriately diluted with distilled water and analyzed for drug content. No precipitation of drug was noted in the filtrate during 24 hours. The results of analysis of naproxen tablet formulations were shown in table – II.

Table II: Results of analysis of Naproxen tablet formulations

Tablet formulation	Label claim per tablet (mg)	% Label claim estimated (mean ± standard deviation)	% Coefficient of variation
I	250	99.51 ± 0.0011	0.155
II	500	99.68 ± 0.005	0.285

Recovery studies:

To study the accuracy, reproducibility and precision of the following method recovery studies were carried out. 15mg and 30mg Naproxen (pure bulk drug) were added to the tablet powder equivalent to 200mg of Naproxen. Each analysis was performed thrice using 0.1M sodium citrate solution and the drug content was calculated and reported in Table III.

Table III: Recovery studies

Tablet formulation	Amount of the drug in tablet powder (mg)	Naproxen pure drug added (mg)	% Recovery estimated (mean ± standard deviation)	% Coefficient of variation
I	200	15	99.9 ± 0.001	0.133
I	200	30	99.82 ± 0.0015	0.189
II	200	15	99.96 ± 0.001	0.136
II	200	30	99.44 ± 0.0011	0.146

RESULTS AND DISCUSSION:

In the present study an attempt has been made to develop Novel spectrophotometric method for the determination of Naproxen in bulk drug and formulations using sodium citrate (0.1M) as hydrotropic agent. The results of solubility studies indicated that, enhancement in aqueous solubility of Naproxen in 0.1M sodium citrate solution, as compared to solubility in distilled water, was more than 40 fold. The developed method was statistically validated for the linearity, precision, LOD and LOQ. The developed method follows the Beer’s – law in the concentration of 20 – 140 mcg/ml at λ_max330nm. The percentage of label claim of proposed method was 99.5 - 99.6%. The % recovery was within range between 99 and 100, which indicates the accuracy of the proposed method. The sensitivity of the method has shown by values of LOD and LOQ respectively 0.428 and 1.428.

CONCLUSION:

The organic solvents such as ethanol, methanol, acetonitrile used widely in spectrophotometric analysis of poorly water soluble drugs are toxic in nature, costlier and responsible for pollution. Inaccuracy in spectrophotometric analysis due to volatility of organic solvents is another drawback. These problems are maximum minimized by development of UV method with hydrotropic agent like sodium citrate. It has UV cut off value 250nm, since it does not interfere above 250nm, therefore, poorly soluble drugs having λ_max above 250nm can be estimated by proposed method, avoiding the use of organic solvents.

The results concluded that the developed spectrophotometric method for determination of Naproxen in bulk and formulations using 0.1M sodium citrate as hydrotropic agent is reliable, accurate, precise, sensitive and eco-friendly. This method can be successfully employed in the routine analysis of Naproxen in bulk drug and dosage formulations.

ACKNOWLEDGMENTS:

The authors are thankful to the Divi’s Laboratories Ltd., India, for providing the gift sample of naproxen and the management of Gokaraju Rangaraju College of Pharmacy for providing the necessary facilities.

REFERENCES

1) R. K. Maheshwari. Spectrophotometric determination of cefixime in tablets by hydrotropic solubilization phenomenon. The Indian Pharmacist, Vol. IV, No. 36, June 2005, p. 63-68.

2) R. K. Maheshwari, S.C.Chaturvedi & N.K. Jain. Application of hydrotropic solubilization phenomenon in spectrophotometric analysis of hydrochlorothiazide tablets. Indian Drugs, 42(8), August 2005, p. 541-544.

3) R. K. Maheshwari. New application of hydrotropic solubilization in the spectrophotometric estimation of ketoprofen in tablet dosage form. The Pharma Review, Vol.3, No. 18, Oct. 2005, p. 123-125.

4) R.K.Maheshwari. Novel application of hydrotropic solubilization in the spectrophotometric analysis of tinidazole in dosage form. Asian J. Chem., Vol. 18, No.1, Jan-March, 2006, p. 640-644.

5) P. N. Sable, G. M. Chaulang, A. V. Bhosale. Novel spectrophotometric estimation of Izetimib, losorton and simvastatin using hydrotropic solubilizing agents. International Journal of Chem Tech Research, Vol.1, No.4, pp 1393-1397, Oct-Dec 2009.

6) Maheshwari, R.K., Pandey, S.P., Ramchandani, U., Gupta, H.M. Analysis of furosemide by application of hydrotropic solubilization phenomenon in solid dosage form. Asian journal of chemistry. 2008: 20(1): 277-281.

7) Maheshwari, R.K., Gupta, H.M., Singh, M., Ramchandani, U., Pandey, S.P. Novel application of hydrotropic solubilization in the spectrophotometric analysis of gatifloxacin in solid dosage form. Asian journal of Chemistry. 2008; 20(1): 241-244.

Received on 19.02.2011 Modified on 10.03.2011

Asian J. Research Chem. 4(5): May, 2011; Page 845-847