INTRODUCTION:

Meclizine, chemically 1-(p-chloro-α-phenylbenzyl)-4-(m-methylbenzyl)piperazine dihydrochloride monohydrate. Meclizine is piperazine-derivative H₁-receptor antagonist, used in the treatment of motion sickness, vertigo, and nausea during pregnancy and radiation sickness. Along with its actions as an antagonist at H₁-receptors, Meclizine also possesses anticholinergic, central nervous system depressant, and local anesthetic effects. Meclizine depresses labyrinth excitability and vestibular stimulation and may affect the medullary chemoreceptor trigger zone⁵.

Meclizine is official in IP, BP, USP and listed in the Merck index and Martindale, the complete drug reference³. Literature survey has indicated that there are no analytical methods for estimation of Meclizine hydrochloride as single component by UV- Visible spectrophotometry^1,2. There is analytical method reported for simultaneous estimation of Meclizine hydrochloride and Nicotinic acid from combined dosage form⁴.

Analysis is an important component in the formulation development of any drug molecule. Hence the present study deals with the development of simple, precise, accurate, sensitive, rapid and economical UV-Visible Spectrophotometric method for estimation of Meclizine in bulk and pharmaceutical formulation.

MATERIALS AND METHODS:

Materials:

Pure Meclizine hydrochloride was obtained as a gift sample from D.K.PHARMA (Mumbai). Methanol (analytical grade) used to dissolve drug. A Shimadzu UV-1700 UV/VIS Spectrophotometer was used with1cm path length and spectral bandwidth of 2nm matched quartz cells. A Shimadzu electronic analytical balance was used for weighing the sample. Meclizine tablet of 25mg were procured from local pharmacy (PNV Tablet)

Method:

Accurately about 10 mg of Meclizine hydrochloride was weighed and transferred to 100 ml volumetric flask, 25 ml of methanol added to dissolve drug then volume was made up with distilled water up to the mark to give the drug stock solution of concentration 100 µg/ml. Aliquots of standard stock solution were pipette out and suitably diluted with distilled water to get final concentration of standard solutions. In zero order spectrum method at n=6 showed a sharp peak at 230nm.(Figure 1). The absorbance difference at n=6(dA/dλ) is calculated by the inbuilt software of the instrument which was directly proportional to the concentration of the standard solution.

Figure 1: Zero Order Spectrum of Meclizine Hydrochloride

Figure 2: First Order Spectrum of Meclizine Hydrochloride

Figure 3-Area under curve of Meclizine Hydrochloride(A₁-228, A₂-234)

The standard drug solution was diluted so as to get the final concentration in the range of 5-35µg/ml and scanned in zero order spectra. The calibration curve of dA/dλ against concentration of the drug showed linearity (Table-2).

Similarly, for first order derivative same method was employed at n=6 showed a sharp peak at 238.5nm (Figure 2). The standard drug solution was diluted so as to get the final concentration in the range of 10-50µg/ml and scanned in first order derivative spectra. The calibration curve of dA/dλ against concentration of the drug showed linearity (Table-3).

The AUC method involves the calculation of integrated value of absorbance with respect to the wavelength between two selected wavelength λ₁ and λ _2. Area calculation processing item calculates the area bound by the curve and the horizontal axis (Figure 3). The horizontal axis is selected by entering the wavelength range over which the area has to be calculated. The wavelength range is selected on the basis of repeated observations so as to get the linearity between area under curve and concentration (Table-4). Suitable dilutions of standard stock solutions. (100µg/ml) of the drug were prepared and scanned in the spectrum mode from the wavelength range 400-200nm and the calibration curve was plotted. All the three methods were checked by analyzing the samples with known concentration. All three methods were validated according to ICH guidelines by carrying out analysis of single component⁶.

For estimation of Meclizine hydrochloride in tablet formulation twenty tablets of the brand were weighed and triturated to fine powder. The powder equivalent to 10 mg of Meclizine hydrochloride was weighed and dissolved in 25 ml alcohol and further diluted with quantity sufficient with distilled water. It was kept for ultra sonification for 45 min this was then filtered through whatman filter paper no. 41 to get stock solution of concentration of 100µg/ml. Various dilution of the tablet solution were prepared and analyzed for six times and concentration was calculated by using the calibration curve (Table-5). Recovery study were carried out at three different levels i.e. 80%,100%, and 120% by adding the pure drug (8, 10 and 12mg respectively) to previously analyzed tablet powder sample, from the amount drug found, percentage recovery was calculated (Table-7).

RESULT AND DISCUSSION:

All the three methods A, B and C for estimation of Meclizine hydrochloride in single component form were found to be simple, accurate and reproducible. Beer-Lambert’s law was obeyed in the concentration range of 10-60µg/ml for first order and area under curve method and 5-35µg/ml for zero order derivative spectra (Table-1). The validation of the proposed method was further confirmed by recovery study data clearly indicate the reproducibility and accuracy of method. The value of standard deviation was satisfactory (Table-6). The recovery values for Meclizine hydrochloride ranged from 98.05 to 101.07 % (Table-7).

Table 1: Optical characteristics and other parameters for Meclizine hydrochloride.

Parameters	Method A	Method B	Method C
max (nm)/wavelength range (nm)	230	238.5	234-228
Beer’s – Lambert’s range (µg/ml)	5-35 (µg/ml)	10-60(µg/ml)	10-60(µg/ml)
Coefficient of correlation (r² )	0.9994	0.9994	0.9995
Regression equation : Y = mx + c	0.0259x-0.0038	-0.0025+.0004	0.1893x-0.0684
a – Slope (m)	0.0259	-0.0025	0.1893
b – Intercept (c)	-.0038	0.0004	-0.0684
LOD	0.0229	0.33	0.0038
LOQ	0.694	1	0.0118
Molar absorptivity	5.2*10²	1.18*10³	3.94*10²

A is Zero order derivative with n=6

B is first order derivative spectrum method with n=6

C the AUC method with n=6

Table: 2: Statistical validation by zero order spectrum method

Parameter	Mean*	S.D*	C.O.V.*	S.E.*
_r2	0.9994	0.00018	.018	0.000073
Slope	0.026	.00049	1.88	0.0002
Intercept	0.0	0.0	0.0	0.0

*Average of six readings [n=6]

Table: 3: Statistical validation by First order spectrum method

Parameter	Mean*	S.D*	C.O.V.*	S.E.*
r²	0.9994	0.00025	0.025	0.0001
Slope	-0.0027	0.09	3333	0.036
Intercept	0.0	0.0	0.0	0.0

*Average of six readings [n=6]

Table: 4: Statistical validation by Area Under Curve method

Parameter	Mean*	S.D*	C.O.V.*	S.E.*
r²	0.9995	0.00023	0.023	0.00009
Slope	0.1893	0.00000007	0.000037	2.9*10^-8
Intercept	0.0	0.0	0.0	0.0

*Average of six readings [n=6]

Table no 5: Analysis of tablet formulation

Sr No	Tablet sample	Amount Present(mg/Tab)	Amount Found (mg/Tab)	Percentage of label claim
1	T₁	10	10.05	100.5
2		10	9.85	98.5
3		10	10.14	101.5

Table no 6: Statistical evaluation of tablet formulation

Sr.No	Tablet Sample	% Mean	S.D	C.O.V	S.E
1	T₁	100.16	1.2	1.243	0.716

Table no 7: Recovery studies

Ingredient	Level of addition	Tablet amount	Amount added	Amount recovered	% recovery	Average recovery
Meclizine	80	10	8	17.65	98.05	99.43
	100	10	10	20.34	101.7
	120	10	12	21.68	98.54