INTRODUCTION:

Antihistamine are drugs that block the action of histamine (a compound released in allergic inflammatory reactions) at the HI receptor sites, responsible for immediate hypersensitivity reactions such as sneezing and itching. Members of this class of drugs may also be used for their side effects, including sedation and antiemesis (prevention of nausea and vomiting). Cetirizine hydrochloride is non sedating antihistamine with long acting activity for treatment of urticarial and rhinitis [1]. Cetirizine Hydrochloride is chemically [2-[4-[(4-chlorophenyl) phenyl methyl]-1-peperazinyl] ethoxy] acetic acid.

It is a non sedative second generation anti histamine drug used in the treatment of seasonal allergic rhinitis, perennial allergic rhinitis and chronic urticarial and also used as adjuvant in seasonal asthma. It acts as a selective antagonist of the histamine H₁receptor.

Cetirizine hydrochloride is a member of the diphenylmethylpiperazine group of antihistamines. The BP suggested a potentiometric titration method for determination of cetirizine hydrochloride and its pure form; while it recommended an HPLC method for both cetirizine oral solution and Tablets [2]. Different analytical procedures were reported for its determination including HPLC [3-6], HPTLC [7], capillary electrophoresis [8] and spectrophotometry [9].

From the literature survey, it was found that many chromatographic methods [HPTLC and RP-HPTLC] have been reported for cetirizine Hydrochloride in their dosage form [10-17]. Number of analytical methods for quantitative determination of cetirizine dihydrochloride alone or in combination with other drugs. Some of these methods include spectrophotometry [18], RP-HPLC [19,20] and TLC [21]. Many methods are specified for the determination of cetirizine as individual and combined dosage form with other combination of drugs and also in biofluid viz., UV-Visible Spectrophotometry [22], HPLC [23,24], HPTLC [25].

Literature survey revealed that no simple UV method has been reported to the best of our knowledge. Hence in the current study an attempt has been made to develop 3 simple and sensitive spectrophotometric methods, which is selective, precise, rapid, reproducible, and economical. Which doesn’t need any costly reagents or other tedious procedures for estimation of the cetirizine Hydrochloride in tablet dosage form.

MATERIALS AND METHODS:

A double beam UV- Visible spectrophotometer was used. Absorption spectra of both test and standard solutions were recorded over the wavelength range of 200-400nm using 1cm quartz cell. Cetirizine hydrochloride was supplied as gift sample, all other chemicals and reagents used were of analytical grade.

Preparation of standard stock solution:

Method 1:

Cetirizine hydrochloride stock solution was prepared by dissolving 40 mg of the drug in 100ml methanol and further dilution was carried out in methanol to achieve the required concentrations.

Method 2:

Accurately weighed about 50mg of Cetirizine hydrochloride was transferred to 100ml volumetric flask and 50ml of distilled water was added to dissolve the drug and diluted up to the mark with distilled water, to get 500μg/ml of Cetirizine hydrochloride.

Method 3:

Accurately weighed about 50mg of Cetirizine hydrochloride was transferred to 100ml volumetric flask and the drug was dissolved with methanol(10ml) and diluted up to the mark with 0.1 N NaOH, to get 500μg/ml of Cetirizine hydrochloride.

Detection of Absorption Maxima:

For the selection of analytical wavelength, standard stock solution of Cetirizine hydrochloride prepared was scanned in the range of 200-400nm in 1cm cell against suitable solvent as a blank. The UV spectrum obtained exhibits absorption maxima (λ max) at 238nm (method 1) and 230nm (method 2 and 3)

Preparation of sample solution:

Method 1:

Cetirizine hydrochloride sample solution was prepared by dissolving tablet equivalent to 40mg of each the drug in 100ml methanol and further dilution was carried out to achieve the required concentration. Several dilutions of stock solutions were prepared to give concentration of 80-90μg/ml. The amount of Cetirizine was determined from calibration curve.

Method 2:

A quantity of tablet powder equivalent to about 10mg of Cetirizine hydrochloride was transferred to 100ml volumetric flask, 60ml of distilled water was added to dissolve drug and volume was then made up to the mark with distilled water. The resulting solution was mixed and filtered through whatmann filter paper No.42. From the filtrate, 5ml of solution was diluted to 25ml with distilled water so as to obtain final concentration of about 20μg/ml.

Method 3

Tablets were weighed and crushed to fine powder, average weight was determined. An accurately weighed quantity of tablet powder equivalent to 25mg of Cetirizine hydrochloride was dissolved in 25ml methanol under stirring, filtered and diluted to 100ml in a volumetric flask by 0.1N NaOH. Further dilution was carried to achieve required concentration.

RESULTS AND DISCUSSION:

The wavelengths of absorption maxima determined for drug Cetirizine hydrochloride showed maximum absorbance at 238nm (Method 1) and 230nm (Method 2 and 3), with reference to British Pharmacopoeia and Indian Pharmacopoeia.

Absorption spectra of Cetirizine Hydrochloride:

Method 1:

From the calibration plot of Cetirizine HCl at the absorption maximas, the linearity was observed in the concentration range 2-20μg/ml for Cetirizine HCl. Coefficient of correlation (R) was found to be 0.999 for Cetirizine HCl as given in optical characteristics. The high value of correlation coefficient (R) also indicates good linearity of calibration curve for this drug.

As per the ICH guidelines, the method validation parameters studied at 238nm (Method 1) were linearity, accuracy, precision and assay of drug. Precision studies were carried out to study the intraday and interday variations of the responses. Instrumental precision study was carried out by repeatability study. The low RSD values and LOD and LOQ values indicate that the method precise and sensitive. Optical characteristics data are given in table 1.

Method 2:

The method discussed provides a convenient and reliable way for quantitative determination of Cetirizine in a dose tablet formulation. Wavelength of maximum absorbance for Cetirizine 230nm is selected for quantitative determination. As per ICH guidelines the method validation parameters checked were linearity, accuracy, precision, LOD and LOQ.

Linearity for Cetirizine was observed in concentration range of 12-60μg/ml and correlation coefficient was always greater than 0.9988 for the drug. Percent label claim for Cetirizine hydrochloride in tablet analysis, was found in the range of 98.99% -100.94%. Percent recovery for Cetirizine hydrochloride was found in the range of 99.38% to 100.64% with standard deviation well below indicating accuracy of the methods intraday and interday precision studies were carried out by analysing tablet formulation. Percent RSD for intraday and interday precision studies for the drug was well within the acceptable range (< 2%), LOD and LOQ were found to be 2.95μg/ml and 8.94μg/ml for Cetirizine respectively. Optical characteristics data are given in the table 1.

Method 3:

The absorption maxima 230(λmax) was selected for the analysis of dug in 0.1N NaOH. Linearity was observed in the range 5 -30μg/ml(r2=0.9988) the amount of drug estimated by the proposed method was in good agreement with the label claim. The proposed method was validated. The accuracy of the method was assessed by recovery studies at 3 different levels. Recovery experiments indicated the absence of interference from commonly encounter additives. The method was found to be precise as indicated by the repeatability, interday, intraday analysis, showing % RTSD less than 2. The results did not show any statistical difference between operators, suggesting that method developed was rugged. The results of accuracy and precision are shown. All statistical data proves validity of the method and can be used for routine analysis of pharmaceutical formulation containing single drug. Optical characteristics data are given in table.1.

Table 1:

Optical characteristics	Method 1	Method 2	Method 3
λmax(nm)	238	230	230
Beer- Lamberts law limit(μg/ml)	2-20	12-60	5-30
Regression equation(y=mx+c)	Y=0.032x+0.011
Slope (m)	0.032	0.007	0.010
Intercept(c)	0.011	0.001	0.030
Correlation coefficient(R)	0.999	0.998	0.996
LOD(μg/ml)	0.457	2.95	2.86
LOQ(μg/ml)	1.386	8.94	8.92
Precision(/RSD)
Repeatability	0.381	0.252,0.250
Intraday	0.461	0.235,0.234	101.92
Interday	0.863	0.610,0.610	100.69

The results of SD and RSD and the recovery studies for Cetirizine HCl following method1, 2 and 3 are given in table 2 and 3 respectively.

Table 2:

Methods	Drug	Amt. of drug estimated (mg/tablet)	% label claim	SD	RSD
Method 1	CTZ	9.89	98.99	0.377	0.380
Method 2	CTZ	9.97	99.79	1.427	1.427
Method 3	CTZ	9.98	99.00	1.427	1.427

Table 3:

Method 1

Method 2

Method 3

Level of recovery

Amount of pure added(mg)CTZ

Amount of drug recovered CTZ

% Recovery

Amt.of drug recovered CTZ

% Recovery

Amt.of drug recoverd CTZ

% Recovery

80%

8.1

8.0

8.13

8.10

100.4

101.3

8.09

7.85

99.87

98.12

8.07

8.08

7.92

99.72

99.54

97.99

100%

10.1

10.2

10.0

10.17

10.15

10.13

100.7

99.54

101.3

10.09

10.21

10.02

99.90

100.0

100.2

10.00

10.02

99.89

100.2

120%

12.1

12.0

12.09

12.11

12.10

99.92

100.1

100.8

12.08

11.93

11.82

99.83

98.59

98.50

11.99

11.08

12.00

98.89

98.50

99.58

Mean % recovery SD

RSD

100.5

0.615

99.38

0.781

99.54

0.754

CONCLUSION:

It can be concluded that the proposed UV spectrophotometric methods for determination of Cetirizine hydrochloride is rapid, economical, accurate, precise and reproducible. The utility of the developed methods have been demonstrated by analysis of tablet formulation. Hence, the proposed method can be employed for quantitative determination of Cetirizine hydrochloride in tablet formulation and conduction of analysis is less cost compared to other instrumental methods.

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Received on 15.06.2020 Modified on 10.07.2020

Asian J. Pharm. Ana. 2020; 10(4):185-188.

DOI: 10.5958/2231-5675.2020.00034.4