Spectrophotometric Determination of Oxcarbazepine in Bulk and Pharmaceutical Formulations

 

Ch. Muralikrishna¹*, C. Rambabu²

¹Department of Chemistry, Adikavi Nannaya University, Rajahmundry,-533105, India.

²Department of Chemistry, Acharya Nagarjuna University, Guntur-521201, India

*Corresponding Author E-mail:

 

Two new rapid, simple, sensitive reproducible and economical spectrophotometric methods are described for the determination of Oxcarbazepine (OXC) in bulk form. Both methods are based on the formation of colored complexes due to the action of 4-Amino phenazone and IsoNiconitic Hydrazide on OXC in alcoholic medium. Under optimized conditions, they show an absorption maxima at 440nm (4-AP) and 450nm (INH), with molar absorptivities of 3.824 x10⁴  and 2.838x10⁴ mole^-  cm^-  and sand ells sensitivities  of 0.08474 and 0.13968 per 0.001 absorbance unit for 4-AP and INH, respectively. The color is stable for 5 min after extraction. In both cases Beers law is obeyed between 2.5-12.5 μg/ ml. The proposed method was successfully extended to bulk and Pharmaceutical dosage forms.

 

 

INTRODUCTION:

Oxcarbazepine (OXC) is a novel antiepilepticdrug, which was developed as a second generation and follow-up compound to carbamazepine (CBZ). OXC has similar therapeutic profile to CBZ but produces much less side effects on patients. It is not official in any pharmacopoeia. Chemically Oxcarbazepine is 10, 11-dihydro-10-oxo-5H-dibenz [b ,f ]azepine-5-carboxamide[1]. Clinically it has been used to treat several types of epilepsy [2], [3], [4]. Literature survey reveals determination of oxcarbazepine by chromatographic methods [5], [6], [7]. Most of the reported methods [8‐13], mainly describe the determination of OXC in biological fluids but only a few methods [14, 15] are describing its determination in pharmaceutical formulations.

 

EXPERIMENTAL:

All spectral measurements were made on Elico SL-159 double beam UV-Visible spectrophotometer. An Elico LI-120 Digital pH meter was used for pH measurements.

 

Preparation of reagents:

Oxcarbazepine Stock solution:

A Stock solution was prepared by dissolving 100mg of Oxcarbazepine in purified water and diluting to 100ml with purified water.

 

4-AP solution (BDH 0.5%, 2.45x10^-2M):

Prepared by dissolving 500 mg of 4-AP in 100ml 0f Methanol containing 1% of conc. HCl.

 

INH solution (sd-Fine 0.8%,5.83x10^-3M):

Prepared by dissolving 800mg of INH in 100ml of Methanol containing 1% of conc. HCl.

 

Method-A (condensation):         

Delivered aliquots of standard OCZ solution (0.5 - 3.0ml, 50mg.ml^-1) into a series of 10ml calibrated tubes. Then 3.0ml (5.83 x 10^-3M) of 4-AP was added to each tube and kept aside for 15min. Later the solution in each tube was made up to 10ml with methanol. The absorbance was measured at 440nm against the reagent blank. The amount of OCZ was computed from its calibration graph, shown in figure-1.

 

Method-B (condensation):

Delivered aliquots of standard OCZ solution (0.5 -3.0ml, 50mg.ml^-1) into a series of 10ml calibrated tubes. Then 2.0ml (2.45 x 10^-3M) of INH solution was added to each

tube and heated for 10min at 60^oC. Later the solution in each tube was made up to 10ml with methanol. The absorbance was measured at 450 nm against the reagent blank. The amount of OCZ was computed from its calibration graph, shown in figure-2.

 

Fig- 1: Beer’s Law plot of OCZ with 4-AP (Method-A).

 

Fig- 2: Beer’s Law plot of OCZ with INH (Method-B).

 

Procedure for the assay of Oxcarbazepine in pharmaceutical formulations

An accurately weighed portion of tablet powder equivalent to about 100 mg of Oxcarbazepine [OCZ] was transferred into a 100ml volumetric flask.  Added about 80.0ml of warm chloroform and shaken well for about 20 min. the contents were diluted with chloroform upto the mark and mixed thoroughly. The solution was filtered the filtrate was evaporated to dryness. The residue was used for the preparation of standard solution as shown under standard solution preparation.

 

Nature of color species

The keto group present in the oxcarbazepine reacts with the amino groups of the reagents in the given methods resulting in the formation of color species. The schemes of color species are given below.

 

RESULTS AND DISCUSSION:

The optical characteristics such as absorption maxima, Beer’s law limits, molar absorptivity and sand ell’s sensitivity are presented in Table -1 the regression analyses using the method of least squares were made for the slope. (b) Intercept (a) and correlation(r) obtained from different. Concentrations and the results are summarized in Table – 1. The present relative Standard deviation and percent range of error (0.05 and 0.01 confidence limits) calculated from the six measurements ¾ of the upper Beer’s law limits of Oxcarbazepine are given in Table – 1.

 

The results showed that these methods have reasonable precision. Comparison of the results obtained with the proposed and UV methods for dosage forms (Table - 2) confirm the suitability of these methods for pharmaceutical dosage forms. In order to Justify the reliability and suitability of the proposed methods, known quantities of pure Oxcarbazepine was added to its various preanlysed formulations and the mixture were analyzed by the proposed methods. The results of recovery experiments were analyzed by the proposed methods the results of recovery experiments are also summarized in TABLE–2. The other active in gradients and execipients usually present in pharmaceutical dosage forms did not interfere.

 

Analysis of formulations

Commercial formulations (tablets) containing OCZ were successfully analyzed by the proposed methods. The values obtained by the proposed and reference methods for formulations were compared statistically with F and t tests and found not to different significantly.  The results were summarized in Table-2. Percent recoveries were determined by adding standard drug to prenalysed formulations. The results of the recovery experiments by the proposed methods are also listed.

 

 

Scheme-1

Scheme- II

 

 

TABLE- 1: Optical characteristics, precision, accuracy of the methods proposed in the determination of oxcarbazepine

S.No	Optical Characteristics	4-Amino phenazone(4-AP)	Isonicotinic hydrazide(INH)
1.	µmax (nm)	440	450
2.	Beer’s law limits (µg/ml)	2.5-12.5	2.5-12.5
3.	Molar Absorptivity (mol-1cm-1)	3.824 x104	2.838x104
4.	Correlation coefficient(µ)	0.9995	0.9964
5.	Sandell’s Sensitivity (µg/cm2/0.01absorbance unit)	0.08474	0.13968
6.	Regression equation(y=a+bC) (i)Slope(b) (ii)Intercept (a)	7.033 x10-2 3.6 x10-3	4.86 x10-2 7.0 x10-3
7.	Relative standard deviation	0.8341	1.6096
8.	% of range error   (confidence limit)  0.05level                                                                                      0.01level	0.8755  1.3730	1.6895  1.6492

*Average of six determinations considered

 

TABLE- 2: Assay of Oxcarbazepine in Pharmaceutical Formulations

Formulations*	Amount taken (mg)	Amount found by proposed Methods**		Reference method	Percentage recovery by proposed Methods***
Tablet 1	600	599.95+0.10 F=2.56 t=0.13	599.95+0.12 F=1.77 t=0.12	599.96+0.16	99.48+0. 98	99.48+0.96

*Tablets from four different pharmaceutical companies.

** Average + standard deviation of six determinations, the t-and F-test values refer to comparison of the proposed method with the reference method.

Theoretical values at 95% confidence limit, F = 5.05, t = 2.262

*** Recovery of 10mg added to the preanalysed pharmaceutical formulations (average of three determinations).

 

CONCLUSION:

The proposed methods are found to be simple, sensitive selective, accurate and economical when compared to quantitative methods by HPLC and LC-MS. It can be used in the determination of Oxcarbazepine in bulk drug and its pharmaceutical dosage forms in a routine manner.

 

ACKNOWLEDGEMENTS:

The authors on thankful to M/S Hetero Drugs Limit, Hyderabad for gift sample and. Department of Chemistry, Acharya Nagarjuna University Nuzvid Campus, Nuzvid, for providing additional laboratory facilities.

 

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Received on 21.06.2013       Modified on 10.07.2013

Accepted on 15.07.2013      © AJRC All right reserved