Visible Colourimetric Estimation of Moprolol in Bulk and Mouth Dissolving Tablet Dosage Forms

 

Rekha Rajeevkumar1*, Dr. S. Anbazhagan1 and P. Rajeev Kumar2

1Department of Pharmaceutical Analysis, Karuna College of Pharmacy, Thirumittacode, Palakkad (Kerala) India

2Department of Pharmaceutics, Karuna College of Pharmacy, Thirumittacode, Palakkad (Kerala) India

*Corresponding Author E-mail: rekhavas@gmail.com

 

ABSTRACT:

Simple and sensitive visible spectrophotometric method has been developed for the determination of Moprolol in mouth dissolving tablet dosage forms. The Method is based on the formation of colored species on binding of Moprolol with sodium carbonate, sodium hydroxide followed by Folin – Ciocaltaeu reagent (F/C) to produce blue colored chromogen with absorption maximum at 520 nm and Beer’s law is obeyed in the concentration range of 5-25µg/ml. The developed method was found to be precise and accurate. The results obtained are statistically validated and found to be reproducible.

 

KEY WORDS: Validation, Moprolol, Dimethylformamide (DMF), Spectrophotometric, Folin – Ciocaltaeu reagent (F/C).


 

INTRODUCTION:

Moprolol belongs to β-adrenergic blocking agent that inhibits the adrenergic response mediated through the         β-receptors, chemically Moprolol is1-(2-methoxyphenoxy)-3-[(1-methyl-ethyl) amino]-2-propanol, 1- (isopropyl amino)-3-(O- methoxyphenoxy)-2-propanol1. It is clinically useful in the treatment of ocular hypertension, ischemic heart disease, congestive heart ischemic heart failure and certain arrhythmias2.The drug is not yet mentioned in any official monograph. A thorough literature survey reveals a few analytical method have been reported for the estimation of Moprolol in bulk and pharmaceutical formulation including UV spectrophotometry3, 4,

 

 

RP-HPLC5 method HPLC–GC6,7 for analysis of moprolol in biological fluids and pharmaceutical dosage forms.

Moprolol

 

The present investigation has been undertaken to develop visible spectrophotometric method in which, the colored species obtained by the oxidation followed by complex formation reaction of moprolol with sodium carbonate, sodium hydroxide followed by Folin–Ciocaltaeu reagent (F/C) to produce blue colored chromogen with absorption maximum at 520 nm and Beer’s law is obeyed in the concentration range of 5-25µg/ml.

 

EXPERIMENTAL:

Instrumentation

A Shimadzu UV/visible double beam spectrophotometer (model 1700) with 1cm matched quartz cells were used for all the spectral measurements. Class ‘A’ volumetric glassware were used. Ultrasonicator was used in the initial steps of extraction. Whatman filter paper No.41 was used to filter the solution.

Reagents

All the chemicals used were of analytical grade procured from Qualigens Fine chemicals, Mumbai. Authentic sample of Moprolol was kindly gifted by strides and chemical specialty Ltd Mangalore. As this drug has no marketed formulations yet, we have formulated mouth dissolving tablets (Tablet1 and Tablet 2) by varying the ratio of using most commonly used excipients like starch, MCC, talc and magnesium stearate by keeping the strength as constant (25 mg of Moprolol) and analysed the drug.

(i)      Double distilled water

(ii)     Sodium carbonate (0.2 % w/v in water)

(iii)    Sodium hydroxide (0.1 % w/v in water).  

(iv)    Folin – Ciocaltaeu reagent  

 

Standard and Sample Solutions

25mg of bulk drug was weighed accurately and dissolved in dimethyl formamide (DMF) and made up to the volume 25ml with DMF. Then it was further diluted to a concentration of 100 µg/ml with distilled water.

 

Preparation of calibration curve:

Different aliquots of drug solution were transferred separately into a series of 10ml volumetric flask,then added 0.5 ml of sodium carbonate solution, 1ml of sodium hydroxide and 1ml of Folin – Ciocaltaeu reagent   (F/C) reagent. After addition of various components, the reaction mixture was allowed to stand of room temperature for 15min. the absorbance of blue colored chromogen was measured at 520nm against reagent blank.

 

Assay of Moprolol in tablet formulation

For formulation analysis, twenty tablets of Moprolol each containing 25mg were accurately weighed and powdered. The powder equivalent to 50 mg Moprolol was weighed and dissolved in DMF, sonicated  and the filtrate were taken further diluted with the distilled water to get the concentration with in the linearity range of standard curve. Then to each dilution to the flask 0.5 ml of sodium carbonate solution, 1ml of sodium hydroxide and 1ml of Folin – Ciocaltaeu reagent   (F/C) reagent was added. After addition of various components, the reaction mixture was allowed to stand of room temperature for 15min. the absorbance of blue colored chromogen was measured at 520nm against reagent blank. 

 

Method Validation8

Accuracy of the methods was determined by recovery studies in the tablet formulation of Moprolol. Recovery studies were carried out by addition of known quantities of standard drug solution to pre analyzed sample at different concentration. Also the experiment was repeated 3 times in a day to determine inter day precision and on 3 different days to determine intraday precision. The co-efficient of variance (% CV) was calculated at each concentration level. The reproducibility was confirmed by repeating the methods, taking different glass wares calibrated, different instruments and different analysts and the %RSD was calculated. The proposed method obeys Beer’s law in the concentration of 5-25 µg/ml. In this method R2 was found to be 0.9998, the slope was 0.0260 and the intercept was 0.00628. Limit of quantification (LOQ) and Limit of detection (LOD) were calculated by repeating the blank measurement six times at 520nm. The values were found to be 0.290 and 0.878 are shown in table1 respectively.

 

RESULT AND DISCUSSION:

The proposed methods are simple, rapid and precise. They do not suffer from any interference due to common excipients of tablet. Beer’s Law is obeyed in the concentration range of 5-25 µg/ml respectively. Both the methods were validated in terms of accuracy, precision and reproducibility and the results were recorded in table 2. Values greater than 99.0% indicate that the proposed method is accurate for the drug analysis. The precision of the proposed methods was checked in terms of inter-day and intra-day given in table 3. The ruggedness of the methods was checked by getting the proposed methods performed by different analysts and by using different glass wares calibrated. The values of % RSD less than 1 indicate that the proposed methods are reproducible for the analysis of Moprolol; and results are given in table 4.

 

Table 1: Optical characteristics and other parameters

Parameters

Method

λmax (nm)

Beer’s law limit µg/ml

Molar extinction(l/mol/cm)

Sandell’s Sensitivity (µg/cm2) per 0.001 absorbance unit.

Regression equation

y = mx + c

Slope(c)

Intercept(m)

Limit of detection   (µg/ml)

Limit of quantification

Correlation coefficient

% RSD

520

5-25µg/ml

9.779 x 104

0.03824

 

 

Y=0.0260C+0.00628

0.0260

0.00628

0.290

0.8788

0.9998

0.777

* Y = bC +a where C is the concentration of moprolol in mg/ml and

Y is the absorbance unit

 

 

 

 

Table 2: Assay of Moprolol in tablet formulation

Sample

(Tablets)

Labelled amount

(mg)

Amount obtained(mg)*

Proposed method

% Recovery**

Proposed method

I                             

 

II

25

 

25

24.99 ± 0.202

 

24.81 ± 0.772

 

99.79 ± 0.8087

 

99.25 ± 0.777

 

* Mean ± s.d. of six determinations.

 

Table 3: Interday and Intraday analysis study

Formulation

Interday

Intraday

Amount found* in mg

S.D

% RSD

Amount found* in  mg

S.D

% RSD

Tablet 1

Tablet 2

24.77

24.89

0.122

0.514

0.241

0.342

24.13

24.90

0.338

0.145

0.225

0.944

* Mean of six observations;   SD = Standard deviation; RSD=relative standard deviation.

 

 

Table 4:  Ruggedness for Moprolol formulation by colorimetric method

Parameters

Tablet 1

Tablet 2

Amount found * in mg

S.D

% RSD

Amount found * in mg

S.D

% RSD

Different analyst

Different instrument

Different glassware

24.87

24.81

24.85

0.058

0.014

0.028

0.07

0.569

0.114

24.61

24.95

24.83

0.064

0.221

0.896

0.260

0.136

0.549

* Mean of six observations;   SD = Standard deviation; RSD=relative standard deviation.

 

 

 


The optical characteristics, such as Beer’s law limit, molar absorptivity, Sandell’s sensitivity are recorded in table 1. The regression analysis using the method of last sequence was made for the slope, intercept and correlation co-efficient obtained from different concentration. The results show that the presence of experiments in tablet formulation did not interfere with the final determination of the active component Moprolol. This reveals the potential utility of these developed methods for the routine analysis of Moprolol in pharmaceutical preparations like mouth dissolving tablets.

 

ACKNOWLEDGEMENTS:

The authors wish to thanks Karuna College of Pharmacy, Thirumittacode, Palakkad for providing necessary facilities and to carry over the work. The authors wish to express their gratitude to Strides research and specialty of chemicals Ltd, New Mangalore for providing the authentic sample (drug).

 

REFERENCES:

1.       Budavari S. The Merck Index, 13th edition, Whitehouse Station, NJ: Merck and Co., Inc.: 1998; p.6347.

2.       Goodman and Gilman’s, The Pharmacological Basics of Therapeutics, Pergamon Press, 10th Edn. New York, 2001; 256 - 258.

3.       Rekha Rajeev and Rajeev Kumar. Spectrophotometric determination of moprolol in pure form and pharmaceutical formulations.  Asian Journal of Chemistry, 2010, 22(3); 1769-1772.

4.       Rekha Rajeev Kumar, Rajeev Kumar P and Nagavalli D. Spectrophotometry for quantitative estimation of moprolol in bulk and pharmaceutical preparation. International  Journal of Chem. Tech Research, 2009; 1(4), 1068-1071.

5.       Gianesello V, Brenn E, Figini G and Gazzanigga A. Determination by coupled high-performance liquid chromatography of the beta-blocker levomoprolol in plasma following ophthalmic administration. Journal of Chromatography. 1989; 473(2), 52-343.

6.       Li F, Bi H, Cote M and Cooper S. Identification and determination of the enantiomers of Moprolol and their metabolites in human urine by high-performance liquid chromatography-mass spectrometry. Journal of Chromatography. 1993; 622(2), 187-95.

7.       Desager JP. Gas-liquid chromatographic determination of Moprolol (SD 1601) in human plasma and urine. Journal of high resolution chromatogr.2005; 3(3), 129-132. Code Q2A. Text on Validation of Analytical Methods. ICH Harmonized Tripartite Guideline, 1995; 60:11260.

 

 

 

Received on 17.07.2012        Modified on 29.07.2012

Accepted on 16.08.2012        © AJRC All right reserved

Asian J. Research Chem. 5(10): October, 2012; Page 1207-1209