Tropical Journal of Pharmaceutical Research Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria ISSN: 1596-5996 EISSN: 1596-9827 Vol. 9, Num. 5, 2010, pp. 499-503

Tropical Journal of Pharmaceutical Research, Vol. 9, No. 5, September-October, 2010, pp. 499-503

Research Article

Spectrophotometric Determination of Cilostazol in Tablet Dosage Form

Pawan Kumar Basniwal¹*, Vinesh Kumar¹, Prabhat Kumar Shrivastava² and Deepti Jain³

¹LBS College of Pharmacy, Tilak Nagar, Jaipur –302004, Rajasthan, ²Department of Pharmaceutics, Banaras Hindu University, Banaras, UP, ³School of Pharmaceutical Sciences, Rajiv Gandhi Technical University, Bhopal (MP), India

*Corresponding author: E-mail: pawanbasniwal@gmail.com; Tel: +91-9414788171 (mob).

Received: 8 January 2010 Revised accepted: 21 July 2010

Code Number: pr10060

Abstract

Purpose: To develop simple, rapid and selective spectrophotometric methods for the determination of cilostazol in tablet dosage form.
Methods: Cilostazol was dissolved in 50 % methanol and its absorbance was scanned by ultraviolet (UV) spectrophotometry. Both linear regression equation and standard absorptivity were calculated and both methods were validated as per ICH guidelines. Cilostazol was determined in tablet dosage form using these validated methods.
Results: The λ max of cilostazol was 258.2 nm in 50 % methanol. Beer-Lambert’s law was obeyed in the concentration range of 0 –25 µg/ml-1 and standard absorptivity was 420.2 dL.g.cm-1 . The numerical values for all the validation parameters were within acceptable limits. The results of cilostazol tablet determination by linear regression equation and standard absorptivity methods indicate purity of 100.0 - 102.4 and 98.7 -101.1 % with standard deviations of 0.611 and 0.592, respectively. Comparing the methods at 99 % confidence limit, the F-test value was found to be 1.065.
Conclusion: These validated methods may be useful for routine analysis of cilostazol as bulk drugs, in dosage forms as well as in dissolution studies in the pharmaceutical industry.

Keywords: Cilostazol tablets, UV spectrophotometry, Linear regression equation, Standard absorptivity.

INTRODUCTION

Cilostazol, whose chemical name is 6-[4-(1cyclohexyl-1H-tetrazol-5-y1) butoxy]-3, 4dihydro-2 (1H) – quinolinone (see Fig 1), is a quinolinone derivative that inhibits cellular phosphodiesterase III, and is used for the inhibition of platelet aggregation and as a vasodilator [1-4].

The literature reveals that chromatographic methods are employed in the determination of cilostazol in tablet dosage form and human plasma and, to the best of our knowledge, no spectrophotometric method has yet been reported for this compound in tablet form [56]. However, the degradation profile and RP-HPLC analysis of cilostazol in tablet dosage form has been reported [7]. Compared to chromatographic methods, spectrophotometric methods are suitable for routine analysis because it is economic, rapid, simple, maintenance-free, and show comparable accuracy and precision with HPLC methods. Therefore, the object of the present work was to develop spectrophotometric methods for the determination of cilostazol in tablet form.

EXPERIMENTAL

Instruments, reagents and chemicals

Ultraviolet spectrophotometer (1700 series, Shimadzu) and UV-VIS double beam spectrophotometer 2201 (Systronics) with 1 cm matched quartz cells were used for the measurement of absorbance. Shimadzu-Ax200 electronic balance was used for weighing the samples, and class “A” volumetric glassware were used.

Working standard (WS) of cilostazol was a gift from IPCA Laboratories Ltd, Ratlam, MP, India, while Pletoz^®50 tablets (cilostazol tablets 50 mg) manufactured by Hetero Drugs Ltd, Hyderabad were procured from a local pharmacy. Methanol AR grade (Merck, India) and distilled water were used for analytical work.

Stock A (500 µg/ml cilostazol) was prepared from accurately weighed 50 mg cilostazol WS in 50 % aqueous methanol. It was diluted with the solvent to produce Stock B (50 µg/ml); aliquots of Stock B were further diluted to give concentrations of 5, 10, 15, 20 and 25 µg/ml of cilostazol, respectively. These dilutions were scanned from 300 to 200 nm against 50 % aqueous methanol as blank, and their absorbances observed at 258.2 nm.

Five dilutions of cilostazol were prepared in triplicate and their absorbances were observed at 258.2 nm. From the above observations, the standard absorptivity, A (1%, 1cm), and molar extinction coefficient were calculated.

As per ICH guidelines [8-9], six dilutions in triplicate were used to validate both methods for linearity, accuracy (by recovery studiesstandard addition to pre-analysed samples), repeatability (within day), intermediate precision (days, analyst and instrument variation) and robustness (methanol variation: 45, 50 and 55 %), and statistical parameters were calculated for them.

Twenty cilostazol tablets were weighed and finely powdered; a quantity equivalent to 50 mg of cilostazol was dissolved in 100 ml of 50 % aqueous methanol and filtered through Whatman filter paper no. 41 to give Stock P. Stock P was diluted to obtain Stock Q (50 µg/ml). Aliquots of Stock Q were diluted to obtain sample concentrations in the range of linearity. The absorbance values of these sample solutions were observed in a multipoint calibration curve of quantitative mode at the selected wavelength (258.2 nm) to obtain test sample concentration.

The linear regression equation obtained from analyzing standard solutions of cilostazol is shown in Eq 1.

ABC = 0.2069C -0.204 .................................... (1)

It showed an r² = 0.9999 where ABC = absorbance, C = concentration (µg/ml), and r²= correlation coefficient. The standard absorptivity, A (1%, 1cm), and molar extinction coefficient (ε) for cilostazol were 420.23 dlg^-1cm^-1 and 15527.5 1 Mol-^-1 cm^-1 , respectively (see Table 1). These developed methods were validated for various parameters, viz, accuracy, precision (repeatability, intermediate precision for days, instrument and analysts) and robustness. Statistical analysis (SD, CV, SEx and SEσ) for validation parameters are summarized in Table 2. These parameters were less than one. Thus, these parameters show the suitability of the methods.

The validated methods were applied to determine cilostazol in tablet dosage form, and the results were 101.23 % (SD = 0.611) by LRE method, and 99.96 % (SD = 0.592) by SA method. Mean of standard deviation (SEx) and standard error of standard deviation (SEσ) were far less than acceptable limits (see Table 3). Value of coefficient of variance for robustness was within acceptable limits.

The linear regression equation and standard absorptivity methods have been validated as per ICH guidelines, and results of validation parameters were within acceptable limits. Cilostazol was estimated by LRE and SA methods in tablet dosage form with standard deviation of 0.611 and 0.592, respectively. On comparing the two methods using the Ftest, the calculated value of F (1.065) was substantially less than the theoretical value at 99 % confidence value; therefore, the methods have comparable precision. Impurities or any other interfering substances with λ max close to that of cilostazol (258.2 nm) would adversely affect the accuracy of the developed methods.. Further study on possible interfering substances will need to be carried out.

The developed methods for cilostazol are simple, rapid and economical with acceptable accuracy, precision, reproducibility and are robust to slight variations in experimental conditions. Thus, the validated methods may be used for routine analysis of cilostazol as the bulk drug and in tablets and other dosage forms where excipients will not interfere spectrally.

1. Hashiguchi M, Ohna K, Nakasawa R, Kishino S, Mochizuki M, Shiga T, Cardiovas Drugs and Therapy, 2004; 18: 211-217.
2. Sweetman SC, Ed, In: Martinadale: The CompleteDrug Reference, 33^rd Edn, Pharmaceutical Press, USA, 2002; Vol I, pp 258-860.
3. Kishida M, Watanabe K, Tsuruoka T. Effects of cilostazal in patients with bradycardiac arterial fibrillation. J Cardiol, 2001; 37: 27-33.
4. Madias JE. Cilostazol: an “intermittent claudicatio”remedy for management of third degree AV block. Chest, 2003; 123(4): 979-982.
5. Bramer SL, Tata PN, Vengurlekar SS, and Brisson JH. Method for the quantitative analysis of cilostazol and its metabolites in human plasma using LC/MS/MS. J Pharm Biomed Anal, 2001; 26(4): 637-650.
6. Lestari AD, Palupi T, Okarina B, Mochammad GY, Indrayanto G. HPLC determination of cilostazol in tablets and its validation. J Liquid Chrom Related Technol, 2004; 27(16): 26032612.
7. Basniwal PK, Srivastava PK, Jain D. Hydrolytic Pharmaceutical for Human Use, Geneva, Jul Degradation Profile and RP-HPLC Estimation 2000). of Cilostazol in Tablet Dosage Form. Indian J 9. ICH “Validation of Analytical Procedure: Pharm Sci, 2008; 70(2): 222-224. Methodology”(International Conference on
8. ICH “Text on Validation of Analytical Procedures”Harmonization of Technical Requirements for (International Conference on Harmonization of Registration of Pharmaceutical for Human Technical Requirements for Registration of Use, Geneva, Jul 2000).

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