Determination of Buclizine Hydrochloride by Derivative Spectrophotometry and RP-HPLC in Tablet Dosage Form

 

G. Babu1*, Thejonath Kolla1, Prasad K.1, M. Vijayabaskaran2, S. T. Latha3

1 Department of Pharmaceutical Analysis, J. K. K. Nattraja College of Pharmacy, Komarapalayam 638 183, Namakkal Dt. Tamil Nadu

2 Department of Pharmaceutical Chemistry, J. K. K. Nattraja College of Pharmacy, Komarapalayam 638 183 Namakkal Dt. Tamil Nadu

3 Dep. of Pharmaceutical Chemistry, Swamy Vivekanandha College of Pharmacy, Elayampalayam 637 205 Namakkal Dt. Tamil Nadu

*Corresponding Author E-mail: gbabu73@gmail.com

 

ABSTRACT:

A simple and specific UV derivative spectroscopy and RP-HPLC was developed for buclizine hydrochloride. These methods are carried out by using 234 nm as the wavelength and 100% v/v methanol as solvent. Second derivative spectroscopy was developed to minimize the interferences. The linearity ranges were 10-50 mcg/ml for derivative spectroscopy and 1-10 mcg/ml for the RP-HPLC respectively. Chromatographic separation was made on Phenomenex Luna C18 (250 mm 4.6 mm, 5μ) column at room temperature with 1.0 ml/min as flow rate and the injection volume was 20 l. The retention time was found to be 7.15 min. The high recovery and low relative standard deviation confirms the suitability of the methods for the determination of buclizine hydrochloride in pharmaceutical dosage forms.

 

KEYWORDS: Buclizine hydrochloride, UV derivative spectroscopy, RPHPLC, Piperazine derivative, Anti-emetic.

 


INTRODUCTION:

Buclizine hydrochloride (Fig-1) is chemically 1-[(4-chlorophenyl) phenyl - methyl] - 4 - [[4-(1,1-dimethyl ethyl) phenyl] methyl] piperazine and its empirical formula is C28H33ClN2. Molecular Weight is 433.04. It is an antiemetic, antihistamine and also possesses anticholinergic activity. Buclizine is a piperazine-derivative antihistamine, used as antivertigo antiemetic agent. Buclizine is used in the prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness. Additionally, it has been used in the management of vertigo in diseases affecting the vestibular apparatus. Although the mechanism by which buclizine exerts its antiemetic and antivertigo effects has not been fully elucidated, its central anticholinergic properties are partially responsible.

 

Only a very few methods are available for the quantitative analysis of buclizine which include colorimetry1, UV spectrophotometry2 and RP-HPLC3. The accuracy and precision were found to be poor in those methods. Hence to improve those parameters, UV derivative spectroscopy and RP-HPLC were developed with the formulation, Longifene.

 

Fig.-1 Buclizine hydrochloride

 

MATERIALS AND METHODS:

Chemicals and Solvents:

Buclizine hydrochloride

Methanol HPLC grade (Qualigens Fine Chemicals, Mumbai)

Water HPLC grade (Qualigens Fine Chemicals, Mumbai)

 

Instruments used:

Shimadzu electronic balance

Elico pH meter

Soltec ultra sonicator

Millipore - solvent filtration unit

UV-visible spectrophotometer (Lab India 3000),

Shimadzu HPLC system

 

Mobile phase:

100% v/v methanol was used as the mobile phase.

 

UV derivative spectroscopy4:

Stock solution:

100 mcg/ml stock solution was prepared by dissolving 10 mg of buclizine hydrochloride in to a 100 ml standard flask and the volume was made up to the mark with methanol to get a concentration of 100 g/ml of solution.

 

Sample solution:

From the stock solution 3 ml of solution was pipetted into 10 ml standard flask and diluted with methanol to get a concentration of 30 g/ ml.

 

Method optimization:

By using the 100% v/v as mobile phase the derivative spectroscopy was performed. As the interferences were observed in the normal and first derivative spectroscopy, to minimise such interferences the second derivative spectroscopy was performed and the maximum wavelength was found to be 234 nm (fig-2).

 

Figure 2 Second derivative spectrum of buclizine hydrochloride

 

Figure 3 Linearity curve of buclizine hydrochloride

 

Method validation:

The UV derivative spectroscopy method was validated in terms of linearity, accuracy, precision of the sample. The linearity of the method was determined by injecting various concentrations 10-50 mcg/ml of buclizine hydrochloride, and the absorbance was measured at 234 nm. From the calibration curves (Fig-3) the correlation coefficient was found as 0.994. Recovery studies were carried out at 80% and 100% level and the contents were determined. The intraday and inter day precisions are also determined and the % RSD was calculated. The precision was found to be not more than 2%. Stability studies were also performed along with the LOD and LOQ.

 

RP-High performance liquid chromatography5:

Stock solution:

100 mcg/ml solution was prepared as stock solution by dissolving 10 mg of buclizine hydrochloride in to a 100 ml standard flask and the volume was made up to the mark with methanol to get a concentration of 100 g/ml of solution.

 

Sample solution:

From the stock solution 0.5 ml of solution was pipetted into 10 ml standard flask and diluted with methanol to get a concentration of 50 g/ ml.

 

Method optimization:

The optimised chromatographic conditions are 234 nm as wavelength, 1 ml/min as flow rate, and injection volume was 20 l (Fig-4).

 

Figure 4 Chromatogram of buclizine hydrochloride

 

Figure 5 Linearity curve of buclizine hydrochloride

 

Method validation:

The RP-HPLC method was validated in terms of linearity, accuracy, precision of the sample. The linearity concentrations are 1-10 mcg/ml. From the calibration curves(Fig-5) the correlation coefficient was calculated as 0.999. The precision studies were also done where the % RSD was < 2%. The recovery studies were determined for 80% and 100%. The robustness and ruggedness also performed. Finally the LOD and LOQ were determined.

 

RESULTS AND DISCUSSION:

UV derivative spectroscopy:

Estimation of buclizine hydrochloride by second derivative spectroscopy was achieved using UV-Vis double beam spectrophotometer. The normal spectra of buclizine hydrochloride was recorded which shows the interference in wavelength. Hence, the second derivative spectroscopic method was developed which showed the λmax at 234 nm. The stock solution of 100 g/ml was prepared with methanol. The standard solutions were prepared and the absorbance vs wavelength was recorded. The linearity was attained in the concentration range of 10-50 g/ml. The slope, intercept and correlation coefficient were found to be 15378.7, 800.5 and 0.994 respectively. The amount of buclizine hydrochloride present in the formulation was found to be 99.92%. The recovery studies were carried out at 80% and 100% level and the reports found to be 98.95%. The precision results of the solution showed that the % RSD was less than 2%, in both intra and inter day precision. The LOD and LOQ were found to be 1.9796 and 5.9988 respectively. The stability studies were also performed.

 

Table 1 Summary of validation parameters of buclizine.

S. No

Validated

Parameter

Results

UV derivative spectroscopy

HPLC

1

Linearity

R2 = 0.994

R2 = 0.999

2

Range

10-50 g/ml

1-10 g/ml

3

Intraday precision (% RSD)

1.45

0.160

4

Interday precision (% RSD)

0.034

0.195

5

Accuracy (% Recovery)

98.95

99.03

6

LOQ

1.9796 g/ml

50 ng/ml

7

LOD

5.9988 g/ml

165 ng/ml

 

RP-High performance liquid chromatographic method:

In RP-HPLC method, optimization of chromatographic parameters was done and 100% v/v methanol was selected as a single mobile phase as it gave a good symmetrical peak with a retention time of 7.154 min. Buclizine hydrochloride showed good linear relationship in concentration range of 1-10 g/ml with a correlation coefficient as 0.999. The amount of buclizine hydrochloride present in the formulation was calculated and reported as 99.91%. The recovery studies were carried out at 80% and 100% level and the reported as 99.03%. The precision results of the solution showed that the % RSD was less than 2%, in both intra and inter day precision. LOD and LOQ were found to be 0.05 g/ml and 0.8 g/ml. No additional peak at the retention time of buclizine hydrochloride for placebo and oxidative degradation study, showed specificity of the methanol. The developed method was validated as per ICH guidelines and the results are reported in Table 1.

 

CONCLUSION:

The proposed analytical methods are simple, rapid, selective, precise and accurate. As the developed methods were validated as per ICH guidelines, these methods can be used for the routine analysis.

 

BIBLIOGRAPHY:

1.       Siddiqui Farhan et. al. Optimization of quantitative analysis of buclizine hydrochloride using UV spectrophotometry in bulk drug and dosage formulations. Medicinal Chemistry Research. 20(1); 2011: 121-124.

2.       Medikondu Kishore et. al. Rapid determination of Ziprasidone and Buclizine Hydrochloride in Pharmaceutical Formulations (Tablets) by Simple Spectrophotometric Method. International Journal of Pharma Sciences and Research. 1(10); 2010: 438-444.

3.       Arayne MS et. al. Simultaneous determination of gliquidone, fexofenadine, buclizine, and levocetirizine in dosage formulation and human serum by RP-HPLC. Journal of Chromatographic Science. 48(5); 2010: 382-385.

4.       Day RA and Underwood AC. Quantitative Analysis of Drugs in Pharmaceutical Analysis, 6th Ed, Prentice- Hall of India Pvt. Ltd., New Delhi. 1993, pp. 338-341.

5.       Ewing GW. Instrumental Methods of Chemical Analysis, 5th Ed., MC Graw Hill Book Co., New York. 1978, p. 61.

 

 

 

Received on 05.05.2011 Modified on 18.05.2011

Accepted on 28.05.2011 AJRC All right reserved

Asian J. Research Chem. 4(8): August, 2011; Page 1350-1352