INTRODUCTION:

Analytical methods are required to characterize drug substances and drug products composition during all phases of pharmaceutical development. Development of methods to achieve the final goal of ensuring the quality of drug substances and drug products must be implemented in conjunction with an understanding of the chemical behaviors and physicochemical properties of the drug substance. This determination requires highly sophisticated methods and instruments like Spectrophotometer.^(1-2)

Fenofibrate 2-[4-(4- chlorobenzoyl) phenoxy]-2- methyl-propanoic acid, 1- methylethyl ester is an antihyperlipidaemic drug, belongs to fibrates. It acts mainly by decreasing serum triglycerides; it has variable effects on LDL-cholesterol. Fenofibrate is used in hyperlipdaemias of type II a, II b, III, IV and V in patients who have not respond adequately to the dietand other appropriate measures. It may also reduce the risk of coronary heart disease events in those with low HDL-cholesterol or with raised triglycerides.⁽³⁾

Metformin hydrochloride chemically 1, 1- dimethlybiguanide hydrochloride is white crystalline powder, hygroscopic and freely soluble in water, used as a hypoglycemic drug. Literature survey reveals that methods like HPLC and spectrophotometric have been reported for estimation of the Metformin hydrochloride in pharmaceutical formulations and biological fluids. Official method includes UV spectrophotometric method for estimation of the drug from the tablets. The present work describes the development and validation of a new Spectrophotometric method for estimation of Metformin hydrochloride in bulk and in tablets.⁽⁴⁾

There was only one method has been reported for estimation of fenofibrate and metformine hydrochloride in tablet by absorption correction method, which prompted to pursue the present work. No simultaneous UV spectrophotometric method for fenofibrate and metformine hydrochloride in tablet dosage form in pharmaceutical preparations has been found in literature survey. So the objective of the present work is to develop and validate new analytical methods for simultaneous determination of fenofibrate and metformine hydrochloride in tablet dosage form. This communication forms the first report of two simple, sensitive and reproducible methods for the simultaneous estimation of fenofibrate and metformine hydrochloride from combined dosage form.

MATERIALS AND METHODS:

Instrument: A Shimadzu UV-1700 UV/VIS Spectrophotometer was used with 1 cm matches quartz cell.

Materials:

Gift samples of MET and FENO were procured from Unique Pharmaceutical Laboratories, Ankleshwar and Panacea biotech LTD, Baddi, Dist. Solan (H.P.) respectively. Tablets containing both drugs i.e. Metformine hydrochloride and fenofibrate were purchased from local pharmacy of commercial brand.

Solvent used: Methanol:

Preparation of stock Solution:

FENO (10 mg) and MET(10 mg) were accurately weighed and transferred to two separate 25 ml volumetric flask, dissolved and made up to mark with methanol to obtained stock solution of 400 mgml^-1 each. The stock solutions of both the drugs were further diluted separately with solvent i.e. methanol to obtain the required range of 1-6 mgml^-1 and 3.125-18.75 mgml^-1solution each and scanned in spectrum mode from 400-200nm. The overlain spectra of both the drug obtained (Fig No.1) to determine the l_max. FENO has l_max at 239 nm while MET has l_max at 218 nm.^(5-14)

Method (Simultaneous equation method):

Two wavelengths selected for the method are 218 nm and 239 nm that are absorption maximas of FENO and MET respectively in methanol. The stock solutions of both the drugs were further diluted separately with methanol to get a series of standard solutions of 1-6 mgml^-1 and 3.125-18.75 mgml^-1concentrations. The absorbances were measured at the selected wavelengths and absorptivities (A 1%, 1 cm) for both the drugs at both wavelengths were determined as mean of three independent determinations. Concentrations in the sample were obtained by using following equations-

A1 ay2 – A2 ay1

Cx= -------------------------- ………….. Eq. (1)

Ax1ay2 – ax2ay1

A1 aX2 – A2 aX1

Cy= -------------------------- ………….. Eq. (2)

Ay1ax2 – ay2ax1

Where, A1 and A2 are absorbances of mixture at 218 nm and 239 nm respectively, ax1 and ax2 are absorptivities of FENO and MET respectively and ay1 and ay2 are absorptivities of FENO and MET respectively. Cx and Cy are concentrations of FENO and MET respectively.

RESULTS AND DISCUSSION:

The methods discussed in the present work provide a convenient and accurate way for simultaneous analysis of FENO and MET. In simultaneous equation method, wavelengths selected for analysis were 239 nm for FENO and 218 nm for MET. This selection of wavelengths shown in Fig No. 1 This method linearity were observed in the concentration range of 1-6 mgml^-1 and 3.125-18.75 mgml^-1 for FENO and MET respectively. Percent label claim for FENO and MET in tablet analysis was found in the range of 95% to 105% its shown in Table no 2.The results of proposed methods for estimation of FENO and MET shown in following Tables no 1. This method can be employed for routine analysis of these two drugs in combined tablet dosage form.

Figure 1: Overlain spectra of Fenofibrate and Metformin Hydrochloride in Methanol.

Table No.1: Analytical parameters

Sl. No	Parameter	fenofibrate	Metformine hydrochloride
1.	Beer’s law limits (mgml^-1)	1-6	3.125-18.75
2.	Molar extinction coefficient (mole^-1 cm^-1)	0.0425143	0.0600182
3.	Sandell’s sensitivity (mg/cm²/0.001 absorbance units)	0.02352	0.016661
4.	Regression equation (y)* Slope (b) Intercept (a)	0.9996 0.0424 -0.004	0.9992 0.06010 0.0008
5.	Standard deviation **	0.00195	0.00896
6.	Limit of detection µgml^-1	0.015	0.049
7.	Limit of quantification µgml^-1	0.045	0.14

*y = a + bx; ** Three replicate samples.

Where, x - the concentration in mg/ml. y - Absorbance unit.

Table No.2: Recovery studies data showing amount of drug recovered from sampleSolution and average recovery

Sr no.	Drug name	Amount present in solution (mgml^-1)	Amount found (mgml^-1)	% recovery
1	FENO	6.000	5.98	99.66
2	MET	3.125	3.18	101.82

CONCLUSION:

UV-Visible spectroscopic method for estimation of FENO and MET in bulk and pharmaceutical dosage form was developed. The test solution was prepared using Methanol as a solvent. Prepared test solutions were scanned for determination of absorbance maxima. Absorbance of the test solutions were measured at 218 nm and 239 nm and plotted graphically to get calibration curves. Results revealed that the analytical method was accurate and highly precise.

ACKNOWLEDGEMENTS:

The authors are thankful to the Principal Dr. A. K. Sheth, Department of Pharmacy, Sumandeep Vidyapeeth, Pipariya, Taluka- Waghodiya, Dist. Vadodara, Gujarat for providing necessary facilities and Unique Pharmaceutical Laboratories, Ankleshwar and Panacea biotech LTD, Baddi, Dist. Solan (H.P.) for providing the gift sample of metformine hydrochloride and fenofibrate respectively. We are also thankful to Mrs. Dhanya B. Sen and Ashim Kumar Sen for his moral support and guidance.

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Received on 24.04.2011 Modified on 22.05.2011

Asian J. Research Chem. 4(8): August, 2011; Page 1235-1237