S. Pillai and I. Singhvi*

Department of Pharmaceutical Sciences, M. L. Sukhadia University, Udaipur-313 001, India.

Corresponding Author:
I. Singhvi
Department of Pharmaceutical Sciences, M. L. Sukhadia University, Udaipur-313 001, India.
E-mail: indrajeet_s@yahoo.com
Date of Submission : 21 June 2005
Date of Revision : 23 February 2006
Date of Acceptance : 28 October 2006
Indian J Pharm Sci, 2006, 68 (5): 682-684  

DOI: 10.4103/0250-474X.29652

Abstract

Three simple, rapid and accurate visible spectrophotometric methods have been developed using Orange G dye for the quantitative estimation of citalopram hydrobromide, donepezil hydrochloride and rabeprazole sodium from respective tablet formulations. These developed methods are based on formation of chloroform-extractable coloured complex of drug and dye. The extracted coloured complex shows absorption maxima at 476 nm and linearity in the concentration range of 10-50 μg/ml for citalopram hydrobromide (method I); at 482 nm and linearity in the concentration range of 5-35 μg/ml for donepezil hydrochloride (method II) and at 477.4 nm with linearity in the concentration range of 10-70 μg/ml for rabeprazole sodium (method III). The results of analysis for all three developed methods were validated statistically and by recovery studies.

Citalopram hydrobromide, chemically 1-[3-(dimethylamino)propyl]-1-(4-flurophenyl)-1,3-dihydro -5-iso-benzofuran-carbonitrile hydrobromide, is a recently developed antidepressant drug [1]. Few analytical methods for estimation of citalopram hydrobromide from biological fluid, including GC [2], GLC [3], HPLC [4–5] and capillary liquid chromatography [6], are reported. Donepezil hydrochloride, chemically 2,3-dihydro-5,6-dimethoxy-2-[{1(phenylmethyl) 4-piperidinyl}methyl]-1-H-inden-1-one hydrochloride, is a recently developed anti-Alzheimer drug [7]. Few analytical methods for estimation of donepezil hydrochloride from biological fluid, including LC8 and HPLC9–11, are reported.

Rabeprazole sodium, chemically 2-[[[4-(3-methoxypropoxy) -3-methyl-2-pyridinyl]methyl] sulfinyl]-1H-benzimidazole sodium, is the latest proton pump inhibitor [12] and is used in the management of acid-related disorders. Few analytical methods for estimation of rabeprazole sodium, including HPLC [13], LC-MS [14] and capillary electrophoresis[15], are reported..

In the present work, simple and sensitive visible spectrophotometric methods have been developed using Orange G dye for the estimation of citalopram hydrobromide, donepezil hydrochloride and rabeprazole sodium in the respective tablet dosage forms.

A Systronics UV/Vis double beam spectrophotometer (model 2101) with 1 cm matched quartz cells was used for spectral analysis. All the chemicals used were of analytical grade. Orange G dye (Thomas Baker) solution (0.3% w/v) was prepared in potassium chloride- hydrochloric acid buffer pH 1.2 and extracted several times with chloroform (Qualigens) so as to remove chloroform-soluble impurities. Double-distilled water was used for the preparation of buffer and standard stock solution for all the three drugs.

The tablet samples of citalopram hydrobromide (Celica 10, Ranbaxy Laboratories; Citalop 20, RPG Life Sciences), donepezil hydrochloride (Donecept 5, Protec; Dopezil 10, Ranbaxy Laboratories) and rabeprazole sodium (Rabeloc 10, Cadila; Veloz 20, Torrent) were procured from the local pharmacy.

For method I, in a series of 10 ml volumetric flasks, aliquots of standard drug solution of citalopram hydrobromide (100 μg/ml) in distilled water were transferred and diluted with the same so as to give several dilutions in the concentration range of 10-50 μg/ml of drug. To each dilution (5 ml) taken in a separating funnel, 5 ml of Orange G solution was added, shaken and allowed to stand for 10 min for the formation of coloured complex. The coloured complex was extracted with 5, 3, 2 ml portions of chloroform, the volume of combined chloroform layer was made up to 10 ml and absorbance was measured at 476 nm against a reagent blank. A calibration curve was prepared by plotting concentration versus absorbance.

For method II, in a series of 10 ml volumetric flasks, aliquots of standard drug solution of donepezil hydrochloride (100 μg/ml) in distilled water were transferred and diluted with the same so as to give several dilutions in the concentration range of 5-35 μg/ml of drug. To each dilution (5 ml) taken in a separating funnel, 5 ml of Orange G solution was added, shaken and allowed to stand for 10 min for the formation of coloured complex. The coloured complex was extracted with 5, 3, 2 ml portions of chloroform, the volume of combined chloroform layer was made up to 10 ml and absorbance was measured at 482 nm against a reagent blank. A calibration curve was prepared by plotting concentration versus absorbance.

For method III, in a series of 10 ml volumetric flasks, aliquots of standard drug solution of rabeprazole sodium (100 μg/ml) in distilled water were transferred and diluted with the same so as to give several dilutions in the concentration range of 10-70 μg/ml of drug. To each dilution (5 ml) taken in a separating funnel, 5 ml of Orange G solution was added, shaken and allowed to stand for 10 min for the formation of coloured complex. The coloured complex was extracted with 5, 3, 2 ml portions of chloroform, the volume of combined chloroform layer was made up to 10 ml and absorbance was measured at 477.4 nm against a reagent blank. A calibration curve was prepared by plotting concentration versus absorbance.

For analysis of formulation, 20 tablets each of citalopram hydrobromide (method I), donepezil hydrochloride (method II) and rabeprazole sodium (method III) were accurately weighed and average weight per tablet was determined. The tablets were powdered separately and powder equivalent to 20 mg for each drug was accurately weighed and was extracted four times with 20 ml portions of distilled water. The combined extract was filtered through Whatman filter paper no. 41 into 100 ml volumetric flask. The residue was washed with distilled water and the washings were added to the filtrate. Final volume of filtrate was made up to the mark with distilled water.

For method I and II, 1 ml of filtrate was diluted to 10 ml with distilled water. This was treated as per the respective procedure for the calibration curve, and amount of drug present in the sample was computed from respective calibration curve. For method III, 2 ml of filtrate was diluted to 10 ml with distilled water. This was treated as per the respective procedure for the calibration curve, and amount of drug present in the sample was computed from respective calibration curve.

All the three developed methods were repeated five times for two different strengths of tablet formulations. Results of analysis are reported in Table 1. Recovery studies were carried out for all the three developed methods by addition of known quantity of pure drug sample to preanalyzed tablet sample solution at three different concentration levels. The result of recovery studies is reported in Table 1.

Method Drug Formulation Label claim mg/tab %  of  label claim  estimated* Standard deviation %  recovery** Standard deviation
I

II

III		 Citalopram Hydrobromide
Donepezil Hydrochloride
Rabeprazole Sodium		 Tablet 1
Tablet 2
Tablet 1
Tablet 2
Tablet 1
Tablet 2		 10
20
5
10
10
20		 99.56
99.73
98.90
99.23
99.56
99.66		 0.421
0.411
0.598
0.569
0.568
0.549		 100.2
99.86
99.96
100.1
99.22
99.24		 0.557
0.532
0.601
0.582
0.521
0.505

Table 1: Analysis of Tablet Formulation

The proposed spectrophotometric methods for determination of citalopram hydrobromide, donepezil hydrochloride and rabeprazole sodium from tablet formulation are based on formation of chloroform extractable coloured complex of drug with Orange G dye. The pH required for visible spectrophotometric methods was optimized at pH 1.2. The results of analysis for all three developed methods were close to 100% and standard deviation was satisfactorily low, indicating accuracy and reproducibility of the methods. Recovery studies were satisfactory, which shows that there is no interference from excipients. The developed methods were found to be simple, rapid, accurate and can be used for routine analysis of drug from tablet formulations.

Acknowledgements

The authors thank Dr. Reddy’s Laboratories, Hyderabad, for providing gift sample of donepezil hydrochloride and rabeprazole sodium; and Ranbaxy Laboratories, Dewas, for providing gift sample of citalopram hydrobromide for the present investigation.

References