Scholarly article on topic 'Simultaneous estimation of dutasteride and tamsulosin hydrochloride in tablet dosage form by vierordt’s method'

Simultaneous estimation of dutasteride and tamsulosin hydrochloride in tablet dosage form by vierordt’s method Academic research paper on "Chemical sciences"

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Arabian Journal of Chemistry
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{Dutasteride / "Tamsulosin HCl" / "Simultaneous equation method" / "UV–Visible double beam Spectroscopy and Urimax-D tablets"}

Abstract of research paper on Chemical sciences, author of scientific article — P. Giriraj, T. Sivakkumar

Abstract Simple, rapid and accurate new vierordt’s (VI) method or simultaneous equation (SE) method is developed and validated for the simultaneous estimation of dutasteride (DU) and tamsulosin hydrochloride (TA) in pure and pharmaceutical dosage form. The method is based on the measurement of absorbance at two wavelengths 240.6nm and 279.4nm, λ max of DU and TA in methanol respectively. Calibration curves are linear in the concentration ranges 20–40μg/ml for DU and 16–32μg/ml for TA. LOD, LOQ, precision and recovery studies are calculated. The proposed method is successfully applied for simultaneous estimation of DU and TA in pure and pharmaceutical dosage form.

Academic research paper on topic "Simultaneous estimation of dutasteride and tamsulosin hydrochloride in tablet dosage form by vierordt’s method"

Arabian Journal of Chemistry (2013) xxx, xxx-xxx

King Saud University Arabian Journal of Chemistry

www.ksu.edu.sa www.sciencedirect.com

ORIGINAL ARTICLE

Simultaneous estimation of dutasteride and

tamsulosin hydrochloride in tablet dosage form by vierordt's

method

P. Giriraj, T. Sivakkumar *

Department of Pharmacy, Faculty of Engineering and Technology, Annamalai University, Chidambaram 608002, Tamil Nadu, India Received 3 December 2012; accepted 13 July 2013

KEYWORDS

Dutasteride; Tamsulosin HCl; Simultaneous equation method;

UV-Visible double beam Spectroscopy and Urimax-D tablets

Abstract Simple, rapid and accurate new vierordt's (VI) method or simultaneous equation (SE) method is developed and validated for the simultaneous estimation of dutasteride (DU) and tamsulosin hydrochloride (TA) in pure and pharmaceutical dosage form. The method is based on the measurement of absorbance at two wavelengths 240.6 nm and 279.4 nm, ^^ of DU and TA in methanol respectively. Calibration curves are linear in the concentration ranges 20-40 lg/ml for DU and 16-32 lg/ml for TA. LOD, LOQ, precision and recovery studies are calculated. The proposed method is successfully applied for simultaneous estimation of DU and TA in pure and pharmaceutical dosage form.

© 2013 Production and hosting by Elsevier B.V. on behalf of King Saud University.

1. Introduction

Dutasteride is a 4 - azasteroid compound, chemically it is 5a,17b-N-{2,5 bis(trifluoromethyl)phenyl}-3-oxo-4-azaand-rost-1-ene-17-carboxamide (Scheme 1). It is a selective inhibitor of both the type 1 and type 2 isoforms of steroid 5 alpha-reductase, an intracellular enzyme that converts testosterone to dihydrotestosterone. It is used in the treatment of

benign prostatic hyperplasia (Budavari, 2001; Sweetman, 2002; Marberger, 2006).

Tamsulosin HCl is a selective antagonist at alpha-1A and alpha-1B-adrenoceptors in the prostate, prostatic capsule, prostatic urethra, and bladder neck. Blockage of these receptors causes relaxation of smooth muscles in the bladder neck and prostate, and thus decreases urinary outflow resistance in men. It is chemically (-)-(R)-5-[2-[[2-(O-Ethoxy-phenoxy)ethyl]amino]propyl]-2-methoxybenzenesulfonamide monohydrochloride (Scheme 2), (Budavari, 2001; Sweetman, 2002; Ichioka et al., 2004).

Detailed literature survey was carried out and revealed that very few analytical methods have been reported for the estimation of DU and TA individually and in combination with other drugs like UV (Choudhari et al., 2012; Pande et al., 2009; Kamila et al., 2010), HPTLC (Dipti B. Patel et al., 2011; Bari et al., 2011), RP-HPLC (Dipti B. Patel et al., 2010), LC-MS/ MS (Agarval et al., 2008; Rahkonen et al., 2007) and chiral

* Corresponding author. Tel.: +91 9443988722; fax: +91 04144239738.

E-mail address: Sivat27@rediffmail.com (T. Sivakkumar). Peer review under responsibility of King Saud University.

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Elsevier I Production and hosting by Elsevier

1878-5352 © 2013 Production and hosting by Elsevier B.V. on behalf of King Saud University. http://dx.doi.org/10.1016/j.arabjc.2013.07.013

Scheme 1 Structure of Dutasteride.

Scheme 2 Structure of Tamsulosin HCl.

separations (Maier et al., 2005). However the SE method was not reported for the estimation of these drugs in combined dosage form.

1.1. Objective

The objective of the present study was to develop a simple, precise, accurate and rapid SE method for the estimation of DU and TA in pharmaceutical dosage form.

2. Experimental

2.1. Apparatus

Shimadzu 1650 UV-Vis double beam spectrophotometer with uv probe software and 1 cm matched quartz cells were used.

2.2. Materials and reagents

Pharmaceutical grade of dutasteride and tamsulosin HCl was kindly supplied by AN therapeutics, (Pondicherry, India), analytical grade methanol (S.D fine chemical Ltd., Mumbai, India) was used throughout these experiments. The commercial tablets used containing 0.5 mg DU and 0.4 mg TA per tablet were manufactured by cipla Pvt Ltd., (Mumbai, India).

2.3. Standard solutions

Stock solutions of DU and TA were prepared by dissolving in methanol 10 mg of DU and TA separately in a 100 ml volumetric flask, sonicated for 5 min. Final volumes of both the solutions were adjusted with methanol to get stock solutions with the concentration of 100 ig/ml of DU and TA.

Figure 1 Overlain spectra of DU and TA. (a) UV spectrum of DU; (b) UV spectrum of TA.

400 nm (Fig. 1) and the kmax values were found to be 240.6 nm for DU (k1) and 279.4 nm for TA (k2) (Jefferey et al., 1989; Beckett et al., 1997).

The concentrations of drugs in sample solutions were determined by the SE method using the following formula.

Cx = A2ayi - Aiay2/ax2ayi - axiay2 Cy = A1ax2 — A2ax1/ax2ay1 — ax1ay2

Where Cx and Cy are the concentration of DU and TA, ax1 and ax2 are absorptivities of DU at 240.6 nm and 279.4 nm, ay1 and ay2 are absorptivities of TA at 240.6 nm and 279.4 nm, respectively.

2.5. Determination of absorptivity value

The absorptivity of each solution was calculated by using the following formula (Khan et al., 2010):

Absorptivity = Absorbance/conc(gm/100 ml)

The developed method was validated as per ICH (ICH Q2(R1), 2005) guidelines.

3. Results

3.1. Specificity

2.4. Procedure

25 ig/ml solutions of DU and TA drugs were prepared from stock solutions and scanned individually in the range of 200-

Specificity was studied by measuring the absorbance of DU and TA individually at 240.6 nm and 279.4 nm against the blank and comparing the absorbance of drug solutions to the blank. No interference was observed.

Concentration (mcg/ml)

Figure 2 Calibration graph for DU.

Figure 3 Calibration graph for TA.

3.2. Linearity

The absorbances were measured for DU and TA in the concentration range of 20, 25, 30, 35, 40 ig/ml and 16, 20, 24, 28, 32 ig/ml at 240.06 nm and 279.4 nm for both the drugs respectively. Calibration graphs were plotted for DU at 240.6 nm and TA at 279.4 nm. (Figs. 2 and 3 respectively) Absorptivity values were calculated for each concentration and presented (Tables 1 and 2).

3.3. Accuracy

Recovery studies were carried out by measuring the absor-bance of added standard solution of both DU and TA in 50%, 100% and 150% levels to the preanalysed sample solutions at 240.6 and 279.4 nm. The amount of DU and TA was calculated and results are presented in Table 3.

3.4. Precision

Inter and intraday precision studies were done by repeated measurements of the absorbance of standard mixed solution in triplicate in same day and single time for three days respec-

tively by the proposed assay method without changing the method procedure. Percentage RSD was calculated and results are presented in Table 4.

3.5. Ruggedness

A study was conducted to determine the effect of variation in analyst to analyst, lab to lab and instrument to instrument in triplicate measurement as per the assay method. % RSD was calculated for each condition and results are presented in Table 5.

3.6. Robustness

Robustness study was carried out by changing the wavelength in ±1 nm from 240.6 nm to 279.4 nm and the results are presented in Table 6.

3.7. Stability

Stability of drug solutions was determined by keeping the drug solution for nine days at room temperature and the absor-bance of sample solution in each day was measured. Results are presented in Table 7.

Table 1 Absorptivity value for DU.

Concentration (ig/ml) Absorbance Absorptivity Absorbance Absorptivity

V240.60 V240.60 k2-279.40 k2-279.40

20 0.414 207 0.112 56

25 0.517 206.8 0.140 56

30 0.622 207.3 0.168 56

35 0.724 206.8 0.196 56

40 0.837 209.2 0.224 56

Absorptivity for k1 207.4 Absorptivity for k2 56

Table 2 Absorptivity value for TA.

Concentration (ig/ml) Absorbance Absorptivity Absorbance Absorptivity

V240.60 V240.60 k2-279.40 k2-279.40

16 0.045 28.12 0.177 110.6

20 0.056 28.00 0.221 110.5

24 0.067 27.91 0.267 111.2

28 0.079 28.21 0.321 114.6

32 0.09 28.12 0.356 111.2

Absorptivity for k 28.07 Absorptivity for k2 111.6

Table 3 Recovery results for DU and TA.

Concentration (%) Added amount (mg) Amount recovered (mg) Amount recovered (%)

DU/TA DU TA DU TA DU TA

50 0.750 0.600 0.740 0.609 98.69 101.61

100 1.500 1.200 1.192 1.497 99.84 99.38

150 2.250 1.8 1.785 2.244 99.74 99.19

Table 4 Intra day and inter day precision results.

Parameters Sampling time DU TA

Amount present (mg) Amount present (%) RSD% Amount present (mg) Amount present (%) RSD%

Intra day precision 0 h 8th h 16th h 0.5019 0.4997 0.5013 100.38 99.950 100.26 0.0041 0.0067 0.0035 0.3980 0.4010 0.4005 99.500 100.27 100.14 0.0060 0.0074 0.0074

Inter day precision 1st day 2nd day 3rd day 0.5037 0.5015 0.4950 100.75 100.29 99.01 0.0018 0.0025 0.0057 0.4013 0.4005 0.4029 100.33 100.18 100.73 0.0058 0.0081 0.0145

Table 5 Ruggedness results for DU and TA.

Parameters DU TA

Amount present (mg) Amount present (%) RSD% Amount present (mg) Amount present (%) RSD%

Analyst I 0.4990 99.80 0.0028 0.4027 100.67 0.0098

II 0.5002 100.04 0.0047 0.4016 100.39 0.0129

Instrument I 0.5015 100.30 0.0026 0.3979 99.49 0.0135

II 0.4955 99.10 0.0047 0.4027 100.61 0.0193

Table 6 Results observed by changing the wavelength ± nm.

Wavelength (nm) DU Wavelength (nm) TA

Amount present (mg) Amount present (%) RSD% Amount present (mg) Amount present (%) RSD%

239.6 0.4948 98.97 0.0059 241.6 0.4922 98.44 0.0039 278.4 0.3953 98.82 0.0033 280.4 0.3926 98.155 0.0024

Table 7 Stability data for DU and TA.

Day DU TA

Amount present (mg) Amount present (%) Amount present (mg) Amount present (%)

1 0.5004 100.08 0.4084 102.12

2 0.5032 100.64 0.4055 101.39

3 0.4934 98.68 0.4000 100.00

4 0.4964 99.29 0.3955 98.87

5 0.4981 99.50 0.3946 98.66

6 0.4975 999.50 0.3934 98.36

6 0.4979 99.58 0.3902 97.56

7 0.4940 99.89 0.3910 97.75

8 0.4940 98.80 0.3892 97.36

9 0.4916 98.33 0.3889 97.23

3.8. Apply the developed and validated method to the marketed dosage form

20 Urimax-D Tablets were accurately weighed and powdered and the powder weight equivalent to 1.5 mg of DU and 1.2 mg of TA was transferred to a 50 ml volumetric flask separately and sufficient methanol was added to dissolve it. Then the solutions were sonicated for 15 min. Then final volume was adjusted with methanol and filtered by vacuum filtration. The filtrate was centrifuged at 10,000 RPM for 30 min. Then clear supernatant solutions were transferred to a separate flask without disturbing the sediment. Then absorbance was measured at 240.6 nm and 279.4 nm for minimum six times. Amount of DU and TA in each tablet was calculated and results are presented in Table 8.

4. Discussion

The SE method was developed and validated for the simultaneous estimation of DU and TA in pure and tablet dosage forms.

From the linearity study, DU and TA were found to be linear in the concentration range from 20-40 ig/ml to 16-32 ig/ ml. Regression coefficient and slope were calculated from the calibration graph 0.999 and 0.021 for DU and 0.996 and 0.011 TA respectively. Intraday and interday precision was performed by replicate measurement of absorbance of mixed standard solutions and percentage RSD was found to be 0.0047%, 0.0033% for DU and 0.0086%, 0.0093% for TA. The recovery studies were carried out to ensure the reproduc-ibility and reliability of this method by adding a known amount of standard drug to the preanalysed sample in three different levels (50%, 100% and 150%). The percentage recoveries of the three concentrations were found to be close to 100%, indicative of high accuracy. The Limit of Detection and Limit of Quantification were theoretically calculated for DU and TA which were found to be 0.1111 ig/ml, 0.2683 ig/ml and 0.336 ig/ml and 0.8131 ig/ml, respectively. Robustness and Ruggedness were also carried out and percentage RSD was found to be less than 0.5%. Stability of DU and TA in methanol was found to be stable up to 9 days at room temperature.

Table 8 Assay results of tablet dosage forms.

DU TA

Amount present (mg) Amount present (% label claim) Amount present (mg) Amount present (% label claim)

0.512468 102.4937 0.390497 97.62428

0.508616 101.7232 0.401403 100.3507

0.512523 102.5045 0.402444 100.611

0.510556 102.1111 0.398937 99.73417

0.509062 101.8124 0.404173 101.0433

0.506676 101.3353 0.403869 100.9672

0.509984 101.9967 0.40022 100.0551

SD 0.421158 SD 1.281944

% RSD 0.004129 % RSD 0.012812

The developed simple, rapid, sensitive, accurate and economical SE or vierordt's method for the routine quantitative determination of DU and TA in tablet dosage form, will reduce unnecessary tedious sample preparations and the cost of reagents without any interferences and prior separations.

Acknowledgement

Authors are thankful to the UGC-BSR, New Delhi, India, for

providing financial assistance to carry out this work.

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