Spectrophotometric Determination of Cefditoren Pivoxil by Diazotization Coupling Reaction in Solid Dosage Forms

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 based on the diazotization of Cefditoren Pivoxil with nitrous acid (NaNo₂/ HCl) at cold temperature followed by its coupling in-situ with β napthol (Method A) to yield deep purple coloured chromogen, diphenyl amine (Method B) to yield pink coloured chromogen, BMR (Method C) to yield purple coloured chromogen, exhibiting absorption maxima at 542, 506 and 539nm , respectively. Beer’s law was obeyed in the concentration ranges of 20-60, 10-50 and 5-30μg/ml respectively. The coloured chromogen was stable for 3-5hrs. 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, β napthol, diphenyl amine, BMR.

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 β napthol, diphenyl amine, BMR. 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 Laboratories 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 2.0 to 6.0 ml (1ml=100μg/ml) were transferred in to a series of 10ml of volumetric flasks. To each flask 0.5ml of conc. hydrochloric acid, 1 ml of sodium nitrite (0.1% w/v) were added and kept aside for 10min at 0-5⁰C and 0.5ml of ammonium sulphamate (0.5% w/v) is added followed by 0.5ml of β-Napthol solution. The volume was made up to mark with 0.1N HCl. The absorbance of the deep purple coloured product was measured at 542 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 β napthol

Fig 2: Calibration Curve of Cefditoren Pivoxil by β napthol

Method B:

Aliquots Cefditoren Pivoxil ranging from 0.5-3ml (1ml=100μg/ml) were transferred into a series of 10ml volumetric flasks. To each flask 0.5ml of conc. hydrochloric acid and 1 ml of sodium nitrite (1%w/v) were added and kept aside for 10 min at 0-5^oC, then 1 ml of ammonium sulphamate (0.5% w/v) was added and the solution was shaken thoroughly. After 2 min, 2ml of coupling agent, N-(1-napthyl) ethylene diamine dihydrochloride (0.1% w/v) was added and the volumes were made Spectrophotometric Determination of Cefditoren Pivoxil up to the mark with 0.1N HCl. The absorbance of the purple coloured chromogen was measured at 539nm (Fig .3) against reagent blank. The coloured chromogen was stable for 3 hrs. The amount of drug present in the sample was computed from calibration curve (Fig.4).

Fig 3: Absorption Spectrum of Cefditoren Pivoxil By diphenylamine

Fig 4: Calibration Curve of Cefditoren Pivoxil bydiphenylamine

Method C:

Aliquots Cefditoren Pivoxil ranging from 1-5ml of (1ml=100μg/ml) were transferred in to a series of 10ml volumetric flasks. To each flask 0.2 ml hydrochloric acid and 0.5 ml of sodium nitrite (0.1% w/v) were added and kept aside for 10 min at\ 0-5^oC, then 1 ml of ammonium sulphamate (0.1% w/v) and the solution was shaken thoroughly. After 2 min, 0.2ml of diphenylamine (0.25% w/v) were added, the volume was made up to the mark with 0.1N HCl .The absorbance of the pink coloured chromogen was measured at 506 nm (Fig .5) against reagent blank. The colour was stable for 5 hrs at room temperature. 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)	542	506	539
Beer’s law limits (mg/ml)	20-60	10-50	5-30
Molar absorptivity (lit. mol^-1 cm^-1)	7.375X10³	9.627X103	1.87X103
Sandell’s sensitivity (mg/ml 0.001 abs unit)	0.035	0.057	0.028
Regression equation (Y*) Slope (b)	0.0132	0.0143	0.0229
Intercept (a)	0.0590	0.0231	0.1071
Correlation coefficient (r)	0.9997	0.9997	0.9949
% RSD	0.126	0.100	0.1385
Range of error** Confidence limits with 0.05 level	0.1028	0.0369	0.8165
Confidence limits with 0.01 level	0.6952	0.0250	0.5518

*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

199.32

199.19

199.58

199.70

99.66

99.95

99.79

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 BMR

Fig 6: Calibration Curve of Cefditoren Pivoxil by BMR

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 diazotization coupling 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 11.05.2011

Asian J. Research Chem. 4(9): Sept, 2011; Page 1478-1481