Development and Validation of Visible Spectrophotometric Methods for Determination of Cefditoren Pivoxil in Pharmaceutical Formulations

Arvind B. Karadi*, S. Appal Raju, Shobha Manjunath and Venugopal Darak

Department of Pharmaceutical Analysis, HKES’s College of pharmacy, Sedam Road, Gulbarga, Karnataka-585105, India.

*Corresponding Author E-mail: arvindabk@rediffmail.com

ABSTRACT:

Three simple, sensitive spectrophotometric methods (Method A, B and C) are developed, Method A and B are based on the oxidation followed by complex formation with 1, 10 phenanthroline (Method A) to yield blood red coloured chromogen, 2’2 bipyridine (Method B) to yield red coloured chromogen, Method C based on oxidation of drug with potassium ferricynide to yield blue coloured chromogen, exhibiting absorption maxima at 510, 522 and 716nm , respectively. Beer’s law was obeyed in the concentration ranges of 2-10, 50-150 and 10-60μg/ml respectively. The coloured chromogen was stable for 4hrs. These methods were extended to pharmaceutical formulations and there was no interference from any common excepients which are usually present in tablet dosage formulations. The results of analysis have been validated statistically and by recovery studies.

KEYWORDS: Cefditoren Pivoxil, Spectrophotometry, 1, 10 phenanthroline, 2’2 bipyridine, potassium ferricynide.

INTRODUCTION:

Cefditoren Pivoxil is chemically (-)-(6R,7R)-2,2-dimethylpropionyloxymethyl 7-[(Z)-2-(2-aminothiazol-4-yl)-2 methoxy iminoacetamido]-3-[(Z)-2-(4-methylthiazol-5- yl)ethenyl]-8-oxo-5-thia-1 azabicyclo[4.2.0] oct-2-ene-2-carboxylate with molecular formula C₂₅H₂₈N₆O₇S₃ and molecular weight 620.7. It is a pale yellow powder, freely soluble in 0.1N HCl, sparingly soluble in alcohol and practically in soluble in water, it is available as tablets of 200mg^1-2. Cefditoren Pivoxil is a third generation cephalosporin antibiotic for oral use, indicated for the treatment of mild and moderate infections in adults and adolescents which are caused by susceptible strains of the designated microorganisms used to treat community acquired pneumonia, transilities etc^3-8 . It is not official in any pharmacopeia. Spectrophotometric analytical reports are not found in literature for its quantitative estimation in bulk drug and pharmaceutical dosage forms. The present investigation has been undertaken to develop three simple, sensitive and accurate spectrophotometric methods using 1,10 Phenanthroline, 2’2 Bipyridine, Potassium ferrycynide. Which are essential for routine quality control analysis of pharmaceutical products containing Cefditoren Pivoxil as active constituent.

MATERIALS AND METHODS:

Apparatus:

All spectral measurements were made on Shimadzu 1800 UV-Visible spectrophotometer with 1 cm matched quartz cells were used.

Materials:

Pure drug of Cefditoren Pivoxil was obtained from Ranbaxy labroteries Solon(HP)and commercial formulations were procured from local market.

Preparation of Standard solution:

Stock solution (1mg/ml) was freshly prepared by dissolving 100mg of Cefditoren Pivoxil in 20ml of 0.1 N HCl in a 100 ml volumetric flask and volume was made up to the mark with 0.1 N HCl (1mg/ml) and further diluted with 0.1 N HCl so as to obtain working standard solutions of 250 and 100μg/ml.

Preparation of sample solution:

Twenty tablets were taken, weighed accurately, powdered and mixed thoroughly. An amount equivalent to 100mg of the powdered drug was taken and dissolved in 0.1N hydrochloric acid for all methods and filtered. The filtrate was made up to 100ml with 0.1 N HCl, appropriate aliquots of the drug solution were treated as described above for the determination of Cefditoren Pivoxil.

Procedure:

Method A:

Aliquots of Cefditoren Pivoxil ranging from 0.2 to 1.0 ml (1ml=100 μg/ml) were transferred in to a series of 10ml volumetric flasks. To each flask 1 ml of ferric chloride (0.03 M) and 1 ml of 1,10 PTL (1% w/v) were added, heated on a water bath for 30 min and then cooled to room temperature. The volume was made up to the mark with 0.1 N HCl. The absorbance of the blood red coloured chromogen was measured at 510 nm (Fig 1) against reagent blank. The coloured chromogen was stable for 4 hrs. The amount of drug present in the sample was computed from calibration curve (Fig 2).

Fig 1: Absorption Spectrum of Cefditoren Pivoxil by 1, 10 phenanthroline

Fig 2: Calibration Curve of Cefditoren Pivoxil by 1, 10 phenanthroline

Method B:

Aliquots of Cefditoren Pivoxil ranging from 0.5 to 2.5ml (1ml=100μg/ml) was transferred in to a series of 10ml volumetric flasks. To each flask 1 ml of Ferric chloride (0.03 M) and 1ml of 2, 2’ BPD (0.03 M) were added, heated on water bath up to 30 min, and then cooled to room temperature. The final volume was made up to the mark with 0.1N HCl. The absorbance of the orange red coloured chromogen was measured at 522 nm (Fig 3) against reagent blank. The coloured chromogen was stable for 4 hrs. The amount of drug present in the sample was computed from calibration curve (Fig 4).

Fig 3: Absorption Spectrum of Cefditoren Pivoxil By 2’2 bipyridine

Fig 4: Calibration Curve of Cefditoren Pivoxil by 2’2 bipyridine

Method C:

Aliquots of Cefditoren Pivoxil ranging from 1 to 6 ml (1ml = 100μg/ml) were transferred to a series of 10ml volumetric flasks, To each flasks 1 ml of Ferric chloride (0.03 M), 1 ml of potassium ferricyanide (1%w/v) were added and the volume was made up to mark with 0.1 N HCl. The absorbance of the bluish green coloured chromogen was measured at 716 nm (Fig 5) against reagent blank. The coloured chromogen was stable for 4 hrs. The amount of drug present in the sample was computed from calibration curve (Fig 6).

Table 1: Optical Characteristics and Precision

Parameters	Method A	Method B	Method C
lmax (nm)	510	522	716
Beer’s law limits (mg/ml)	2-10	5-25	10-60
Molar absorptivity (lit. mol^-1 cm^-1)	3.43X10³	2.16X103	8.44X103
Sandell’s sensitivity (mg/ml 0.001 abs unit)	0.035	0.057	0.028
Regression equation (Y*) Slope (b)	0.0229	0.0047	0.0151
Intercept (a)	0.1071	-0.0960	0.0301
Correlation coefficient (r)	0.9999	0.9997	0.9996
% RSD	0.299	0.280	0.232
Range of error** Confidence limits with 0.05 level	0.1227	1.3029	0.1227
Confidence limits with 0.01 level	0.8295	0.8807	0.8295

*Y=bC+a, where Y is the absorbance unit and C is the concentration of Cefditoren Pivoxil in mg/ml,

**Average of eight determinations,

Table-2 Evaluation of Cefditoren Pivoxil in Tablet Dosage formulations.

Label Claim (mg)

Amount of drug obtained by proposed methods (mg)

Reference method UV**

% Recovery*

% Recovery**

by UV

M₁

200

199.83

199.71

199.12

199.70

99.91

99.85

99.56

99.70

*mean of six determinations, ** UV method developed in our laboratory M₁=Tablets from Ranbaxy Laboratories

Fig 5: Absorption Spectrum of Cefditoren Pivoxil By Potassium ferricynide

Fig 6: Calibration Curve of Cefditoren Pivoxil by Potassium ferricynide

RESULTS AND DISCUSSION:

The optical characteristics such as Beer’s law limits, Molar absorptivity, and relative standard deviation were calculated and the results are summarized in Table 1.Regression characteristics like slope, intercept and correlation co-efficient were calculated and are presented in Table 1.Commercial tablets of Cefditoren Pivoxil were successfully analyzed by the proposed methods and the results are presented in Table 2. Comparison of the results obtained with the proposed and UV methods for dosage forms (Table 2) confirms the suitability of these methods for Pharmaceutical dosage forms. To evaluate validity and reproducibility of the methods recovery experiments were conducted and the results are summarized in Table 2. The other active ingradients and excipients usally present in pharmaceutical dosage forms did not interfere.

CONCLUSION:

The proposed spectrophotometric methods for the estimation of Cefditoren Pivoxil are simple, sensitive, accurate and can be used for routine quality control of the drug in bulk as well as its pharmaceutical formulations.

ACKNOWLEDGEMENTS:

The Authors are thank full to Principal, Management, HKES’s College of Pharmacy, Gulbarga Karnataka (India) for providing necessary laboratory facilities to carry out the present work and Ranbaxy laboratories Solon (HP) for providing gift sample of drug for research.

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Received on 06.04.2011 Modified on 09.04.2011

Research J. Pharm. and Tech. 4(8): August 2011; Page 1269-1272