Selective Visible Spectrophotometric Estimation of Ambroxol Hydrochloride in Presence of Cetirizine Hydrochloride in Tablets.

 

Potdar VH1*, Kuchekar BS2 and Patil SS1

1Tatyasaheb Kore College of Pharmacy, Warananagar-416113, Maharashtra, India.

2 MAEER’S Maharashtra Institute of Pharmacy, Kothrud, Pune, Maharashtra, India.

*Corresponding Author E-mail: potdarvicky123@rediffmail.com

 

ABSTRACT

The objective of this work was to develop a simple, accurate, rapid and sensitive method for the estimation of ambroxol hydrochloride in presence of cetirizine hydrochloride in tablets. The estimation is based on the reduction of ferric from ferric nitrate to ferrous ions by the drug (ambroxol hydrochloride),which further in presence of 3-Methyl-2-Benzothiazolinone Hydrazone Hydrochloride (MBTH), to produce red colored complex, measured at 568 nm. The chromogen obeyed linearity over 6-54 mg/ml (r=0.9988) with percent relative standard deviation (% RSD) of 0.16, showing that method has good accuracy and precision.

 

KEYWORDS:  Ambroxol hydrochloride, Cetirizine hydrochloride, MBTH, Ferric nitrate.

 

 

INTRODUCTION:

Ambroxol hydrochloride is metabolite of bromhexine and it is administered as hydrochloride salt1. It is used in a variety of disorders including chronic bronchitis, cystic fibrosis and infants respiratory disorder syndrome2.Chemically it is trans-4-{(2-amino-3,5-dibromobenzyl) amino} cyclohexanol hydrochloride3. Literature survey reveals HPLC4, RP-HPLC5 and UV-spectrophotometric6-7 method for determination of ambroxol hydrochloride in tablets. However no selective visible spectrophotometric method is available for quantitative determination of ambroxol hydrochloride in presence of cetirizine hydrochloride in tablets. The present work describes a simple colorimetric method for the estimation of ambroxol hydrochloride in presence of cetirizine hydrochloride in tablets.

 

In this method the drug (ambroxol hydrochloride) reduces ferric ions from ferric nitrate to ferrous, which further in presence of MBTH, produces red colored complex having absorption maxima at 568 nm. The objective of proposed research work was to develop simple, economic and suitable visible spectroscopic method for routine determination of ambroxol hydrochloride in presence of cetirizine hydrochloride in tablets.

 

MATERIALS AND METHODS:

Instrument: 
A SHIMADZU UV/VIS 1700, a spectrophotometer with 1 cm-matched quartz cells was used for spectrophotometric measurements.

 

Reagents:  

Ferric nitrate (5% in 5% HCl), MBTH (0.3 % in distilled water).Double distilled water was used throughout the experiment.

 

Method:

Preparation of Standard drug solution:  

The standard drug solution was prepared by dissolving accurately weighed bulk drug 20 mg of cetirizine hydrochloride and 60mg of ambroxol hydrochloride in distilled water. This stock solution was suitably diluted with distilled water to get standard drug solution of ambroxol 600 µg/ml and cetirizine 200 µg/ml.The final volume of stock was 100ml.

 

Preparation of Standard curve: 

Aliquots of (0.1to1.5ml) portions of standard drug solution were transferred to a series of 10 ml volumetric flasks. To each of these flasks were added 1.2 ml of ferric nitrate , 1.6 ml of MBTH and the reaction mixture  were heated for two minute on water bath at 1000 C.The content were cooled to room temperature and volume was adjusted to 10 ml with distilled water. The red colored complex obtained were scanned in the range of 200-750 nm. The λmax of solution was found to be 568 nm.

 

The absorbance of these chromogens  were measured at 568 nm against reagent blank. A linear calibration curve was plotted using concentration Vs absorbance. Beer’s law was obeyed in concentration range of 6-54 µg/ml.

Table 1: Optical and regression characters of standard Ambroxol hydrochloride.

Parameters

Value

Absorption maxima (nm)

568

Beers law limit ( µg ml-1 )

6-54

Correlation coefficient (r2)

0.9988

Molar absorptivity (lit mole -1 cm -1)

0.31 × 10 4

Sandell’s sensitivity (µg cm  -2  0.001 -1) AU

0.13

Regression equation

Y= 0.0075 x +0.02

Slope (m)

0.0075

Intercept (c)

0.02

Limit of detection (LOD µg ml-1)

0.1738

limit of quantification (LOQ µg ml-1)

0.5266
 
Table 2: Results of analysis and recovery studies:

Formulations

Label claim (mg)

% Estimated*

% Recovery

Cetzine A

60

99.30

99.08

Relent

60

99.78

99.73

* Mean of 5 determinations.

 

Analysis of tablets: 

Twenty tablets of two pharmaceutical brands Cetzine A (Glaxo-smithkline)and Relent (Dr.Reddy’s lab)were taken and accurately weighed and powdered in a glass mortar. The powder equivalent to 60 mg of ambroxol was weighed and transferred to 100ml volumetric flask. It was dissolved in distilled water and volume made up to 100 ml with distilled water. The solution was filtered through Whatman filter paper no.41 and filtrate was diluted to obtain concentration between linearity range. To this solution ,1.2 ml of ferric nitrate and 1.6 ml of MBTH were added and reaction mixture were heated for two minute on water bath at 1000 C .The solution was allowed to cool at room temperature after heating and then diluted up to 10 ml with distilled water. The absorbance of this sample solution was measured and amount of ambroxol hydrochloride was determined by referring to standard curve.

 

Recovery studies and validation of method 8: 

Recovery studies were carried out by adding a known amount of pure drug to the preanalysed formulation and reanalyzed the mixture by proposed method. From the amount of drug found, % recovery was calculated. The results obtained are given in table 2.

 

Limit of detection (LOD) and limit of quantification (LOQ) were calculated by Eqs. 1, LOD=3.3 δ/s and 2, LOQ=10 δ/s, respectively, were δ is the standard deviation of blank and s is slope of calibration9. The LOD and LOQ were found to be 0.1738 µg/ml and 0.5266 µg/ml, respectively.

 

RESULT AND DISCUSSION:  

Analytical method was developed and validated for the determination of ambroxol hydrochloride in presence of cetirizine hydrochloride in tablets. Recovery studies shows that the excipients used in the formulation of marketed products do not interfere with estimation of drug. Also there is no interference of cetirizine with ferric nitrate, MBTH and ambroxol hydrochloride. Therefore developed method can be used for selective estimation of ambroxol hydrochloride in presence of cetirizine hydrochloride in tablet, on account of its precision, simplicity, accuracy and reproducibility.

 

ACKNOWLEDGEMENTS:

We are grateful to Dr. Reddy’s Lab Ltd, Hyderabad, India, for providing gift sample of drugs for research work.

 

REFERENCES:

1.        The Merck Index XIV, Merck Research Lab, USA, 2006.

2.        Joao LM Santos et al. Determination of Ambroxol in an Automated multi-pumping pulsed flow system. Anal Sci. 2005; 21:461-464.

3.        The British Pharmacopoeia, HM. Stationary Office, London, 2007.

4.        Heinanen M, Barbas C. Validation of an HPLC method for the quantification of ambroxol hydrochloride and benzoic acid in syrup as pharmaceutical form stress test for stability evaluation. J Pharm Biomed Anal. 2001; 24(5):1005-10.

5.        AS Birajdar et al. Simultaneous Analysis of Ambroxol HCl with Cetirizine HCl and of Ambroxol HCl with levo- Cetirizine Dihydrochloride in Solid Dosage Forms by RP-HPLC. Acta Chromatographica. 2008; 20(3): 411-421.

6.        N.M.Bhatia et al. Spectrophotometric estimation of ambroxol hydrochloride and cetrizine hydrochloride in tablets.Asian J of Pharmaceutics.2008; 2(3):159-162.

7.        Indrayanto G, Handayani R. Quantitative determination of ambroxol hydrochloride in tablets. J Pharm biomed Anal. 1993; 11(8):781-784.

8.        Text on Validation of Analytical Procedures Q2B in; I.C.H.Harmonised Tripartite Guidelines; Nov.1996.

9.        Busaranon K, Suntornsuk W, Suntornsuk L. Comparison of UV spectrophotometric method and high performance liquid chromatography for the analysis of flunarizine and its application for the dissolution test. J Pharm Biomed Anal.2006; 41:158-64.

 

 

 

Received on  27.05.2009         Modified on 25.06.2009

Accepted on 05.07.2009         © AJRC All right reserved

Asian J. Research Chem.  2(3): July-Sept.  2009 page 278-279