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B. Dhandapani et al. / International Journal on Pharmaceutical and Biomedical Research

Vol. 1(1), 2010, 49-53

SPECTROPHOTOMETRIC ESTIMATION

OF PROPAFENONE IN BULK DRUG AND

ITS PHARMACEUTICALFORMULATION

B.DHANDAPANI J.KEERTHI M.BABU NAIK L.LAVANYA

D.L.PRIYAMVADHA K.K MANJEERA

BH.ANUSHA R.V.CELESTIN BABOO

Department of Pharmaceutical Analysis, A.M. Reddy Memorial College of Pharmacy, Petlurivaripalem,

Narasaraopet (Mdl), Guntur District 522601. Andhrapradesh, India.

Three simple, accurate, rapid and sensitive methods developed for the determination of propafenone in bulk

drug and in its tablets by UV Spectroscopy (Method - A), Extractive Spectrophotometric estimation (Method -B)

and Hydrotropic method (Method - C). In Method A propafenone estimated at 301 nm using ethanol as a solvent.The linearity was observed in the concentration range of 20 - 200 g/ml with correlation co efficient of 0.9819. In

Method B extractive spectrophotometric estimation of propafenone using methylene blue and phosphate buffer (PH 8) as an ion pair complexing agent using chloroform as a extractive solvent, the intensity of the resulting bluish

green color of the organic layer was measured at 485 nm. The linearity was observed in the concentration range of

200 - 1000 g/ml with correlation co efficient of 0.9769. In Method C Diphen hydramine citrate solution used as a

hydrotropic agent to dissolve the propafenone which is water insoluble, and it is estimated at 301 nm with the

linearity range and correlation co -efficient of 15 150 g/ml and 0.9985. The result of analysis for all the methodswas validated statistically and by recovery studies.

Key Words : Propafenone, Hydrotropic agent and Extractive Spectrophotometry.

INTRODUCTION

Propafenone is chemically 2'-[2-Hydroxy-3-(propylamino)-propoxy]-3-Phenyl propiophenonehydrochloride, [Fig-1] used as Anti arrhythmic agent1. Propafenone is a Class 1C antiarrhythmic drug with local

anesthetic effects, and a direct stabilizing action on myocardial membranes. The electrophysiological effect ofPropafenone manifests itself in a reduction of upstroke velocity (Phase 0) of the monophasic action potential in

Purkinje fibers, and to a lesser extent in myocardial fibers. Propafenone reduces the fast inward current carried by

sodium ions. Diastolic excitability threshold is increased and effective refractory period is prolonged. Propafenone

reduces spontaneous automaticity and depresses triggered activity. Survey of literature reveals that the drug isdetermined by using GC-MS

2, HPLC

3-5and LC-MS

6, according to our knowledge there is no spectrophtometric

methods has reported for the estimation of propafenone in pharmaceutical formulation. The present study describes

simple, sensitive, accurate, rapid and economical spectrophotometric methods A, B and C for the estimation ofpropafenone in bulk drug and its pharmaceutical formulation.

Fig 1: Structure of Propafenone

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EXPERIMENTAL

ELICO UV Spectrophotometer SL 150 with 1cm matched quartz cells was used for the spectra

measurements.

All the chemicals used were of analytical reagent grade: (i) Ethanol (ii) Chloroform (iii) Diphen

hydramine citrate (iv) All Reagents were prepared by using distilled water.

ASSAY PROCEDURE

METHOD A: Propafenonestock solution was prepared by weighing 100mg of propafenone accurately

and transferring it into a 100 volumetric flask (previously calibrated) and the volume was made up to the mark with

ethanol to get concentration of (1000g/ml) (solution-A). From this aliquots of 0.2ml, 0.4ml, 0.8ml, 1.2ml, 1.6mland 2ml were pipetted out into different 10ml volumetric flasks (previously calibrated) and diluted to 10ml with

ethanol to get concentrations of 20g/ml, 40g/ml, 80g/ml, 120g/ml, 160g/ml and 200g/ml respectively.

Absorbance of resulting solution was measured at 301nm using UV-Visible Spectrophotometer against blank(Ethanol).

Similarly the absorbance of sample solution was measured and amount of Propafenone was determined by

using calibration curve.

METHOD B: Propafenone stock solution was prepared by weighing 100mg of Propafenone,

transferring it to a 100ml volumetric flask and volume was made up to 100ml with ethanol to get a concentration of1000g/ml (Solution-A). From these aliquots of 2ml, 4ml, 6ml, 8ml and 10ml of solution were pipetted out into

different 10ml volumetric flask and diluted to 10ml with ethanol to get a concentration of 200g/ml, 400g/ml,

600g/ml, 800g/ml and 1000g/ml, these are transferred to different separating funnel containing 10ml of

methylene blue, 10ml of chloroform and 1ml of phosphate buffer (PH -8) and shaking for 15 min, the organic layer

has been separated out and the intensity of bluish green color was measured at 485nm against blank.

Similarly the absorbance of sample solution was measured and amount of Propafenone was determined by

using calibration curve.

METHOD C: By using hydrotropic solubilising agent (Diphen hydramine citrate), the drug-propafenone(insoluble in water) is made water soluble due to a complex formation which is completely soluble in water. The

absorbance of resulting solution was measured at 301 nm.

Propafenone stock solution was prepared 250mg of Diphen hydramine citrate was dissolved in 10ml of

distilled water in a 1000ml volumetric flask. Then add 100mg of propafenone to it, and it was heated on a water bath

until a clear solution is formed and volume was made up to 1000ml with distilled water to get a concentration of

1mg/ml (solution A). From this solution an aliquot of 10ml was withdrawn and it was diluted to 100ml withdistilled water to get a concentration of 100g/ml (solution-B).

From Solution-B aliquots of 0.5ml, 1ml, 1.5ml, 2ml, 2.5ml, 3.0ml were pipetted out and diluted to 10ml by

using distilled water to get concentrations of 5g/ml, 10g/ml, 15g/ml, 20g/ml, 25g/ml, 30g/ml respectively.

Absorbance of this solution was measured at 301nm against blank.

Similarly the absorbance of sample solution was measured and amount of Propafenone was determined byusing calibration curve.

ANALYSIS OF FORMULATION

10 tablets of Propafenone (Brand name-Rythmol) of label claim 150mg were weighed. Average weight was

determined. The tablets were finely powdered and equivalent weight equal to 100 mg were calculated based on label

claim and transferred to a 100ml volumetric flask and make up with diphen hydramine citrate solution to get a

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Table-4 (Method A): Recovery Studies

S.No Sample Labelled Amount

(mg)

Concentration

Taken For

Analysis (g/ml)

Amount Of

Substance

(g/ml)

% Label

Claim

1. Tablet 150 60 59.81 99.68

2. Tablet 150 90 91.52 101.683. Tablet 150 120 119.28 99.4

Mean % Label

Claim

100.253

Each Value is a Mean of Six ObservationsTable-5 (Method B): Recovery Studies

S.No Level

Concentration of

standard

used(g/ml)

Concentration of

sample used(g/ml)

Amount

found

(g/ml)

%

Recovery

1. Solution-A 400 400 399.87 99.96

2. Solution-B 600 600 602.74 100.49

3. Solution-C 800 800 801.23 100.27

Mean %Recovery 100.24

Each Value is a Mean of Six Observations

Table-6 (Method C): Recovery Studies

S.No Level

Concentration of

standard

used(g/ml)

Concentration of

sample

used(g/ml)

Amount

found

(g/ml)

%

Recovery

1. Solution-A 120 60 59.81 99.68

2. Solution-B 150 90 87.64 97.37

3. Solution-C 180 120 118.34 98.61

Mean %

Recovery

98.55


RESULTS AND DISCUSSION

Estimation of Propafenone in dosage forms by UV, Visible Spectrophotometry (ExtractiveSpectrophotometry) and hydrotropic solubilisation method was carried out using optimized conditions, the

percentage recovery of drug found in formulations and the results of analysis shows that the amount of drug was in

good agreement with the label claim of the formulation. The proposed method for quantification of Propafenone in

tablets was simple, precise, accurate, rapid and sensitive. The methods are linear in the concentration range reported.The developed methods are free from interference due to the excipients present in the tablets and can be used for

quantitative estimation of Propafenone in tablets. Statistical analysis was carried out and the result of which

satisfactory. The optical characteristics such as absorption maxima, Beers law limits, molar absoptivity and sand

ells sensitivity were reported in Table - 7.

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TABLE-7: Summary of Validation and Statistical Parameters:

S.NO

PARAMETER RESULTS

UV COLORIMETRY HYDROTROPI

C

1 max 301 485 301

2 Linearity range (g/ml) 20-200 g/ml 200-1000 g/ml 15-150 g/ml3 Correlation coefficient (r) 0.9818 0.9769 0.9985

4 R2 0.9641 0.9544 0.9971

5 Intercept 0.03471 0.04405 0.02446

6 Slope 0.003785 0.0004656 0.005939

7 Standard deviation (SD) 0.2880 0.1783 0.3333

8 Standard error (SE) 0.1089 0.07280 0.1260

9 Limit of detection (LOD) (ng/ml) 255.14094 1263.7242 185.19784

10 Limit of Quantification (LOQ)(ng/ml)

760.8982 3829.4674 561.20559

11 Intra day (%RSD) 0.01 0.0055 0.0067

12 Inter day (%RSD) 0.00725 0.0176 0.02695

13 Repeatability (%RSD) 0.0091 0.0091 0.011114 Molar absorptivity 3.73x10-6 6x10-7 6.4x10-6

15 Sandells Sensitivity 0.2678g/ml 1.764 g/ml 0.1565 g/ml

16 Accuracy 100.32% 100.24% 98.55%


The regression analysis using the method of least squares was made for slope (m), intercept (c) and

correlation obtained from the different concentration and the results were shown in Table 7.

The reproducibility and precision of the methods are very good shown by the low values of % RSD.

Recovery studies were close to 100% that indicates the accuracy and precision of the proposed methods and also

indicates non interference from the formulation excipients. The results of analysis were shown Table 7.

In conclusion the developed methods are simple, accurate, sensitive and economical for the routineestimation of Propafenone in bulk drug and its pharmaceutical formulations.

REFERENCES

[1] M.J.O Neil. The Merck Index. 13th edn. Merck Research Laboratories Station, NJ.2006, 1396.[2] Saburo Higuchi, Chizuko Urano & ShigeoKawamura, Determination of plasma protein binding of propafenone in rats, dogs and humans by

highly sensitive gas chromatographymass spectrometry (1985), Journal of Chromatography A, 34 (1): 305-31.

[3] Hollenhors, Th., and Blaschke, G., Direct separation of the enantiomers of propafenone, Di prapofenone and their major metabolites byhigh-performance liquid chromatography on modified cellulose and amylose chiral stationary phases (1991), Journal of Chromatography

A, 585 (2): 329-332.

[4] Michel Prevot, Michel Tod, Josef Chalom, Patrick Nicolas and Olivier Petitjean, Separation of propafenone enantiomers by liquidchromatography with a chiral counter ion (1992), Journal of Chromatography A, 605 (1): 33-39.

[5] Luis Renato Pires de Abreu, Vera Lcia Lanchote, Carlo Bertucci, Evandro Jos Cesarino and Pierina Sueli Bonato , Simultaneousdetermination of propafenone and 5-hydroxypropafenone enantiomers in plasma by chromatography on an amylose derived chiralstationary phase (1999), Journal of Pharmaceutical and Biomedical Analysis, 20 (1-2): 209-216.

[6] Ute Hofmann, Monika Pecia, Georg Heinkele, Karin Dilger, Heyo, K., Kroemer and Michel Eichelbaum,Determination of propafenone andits phase I and phase II metabolites in plasma and urine by high-performance liquid chromatographyelectro spray ionization mass

spectrometry (2000), Journal of Chromatography B: Biomedical Sciences and Applications,748 (1): 113-123.

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