IR Quantification of Alverine Citrate in Bulk and Oral Dosage Form

 

N. Oval, A. Jerad Suresh,  V. Niraimathi *

Department of Pharmaceutical Chemistry, College of Pharmacy, Madras Medical College, Chennai-600003, Tamil Nadu, India.

Alverine is chemically N-Ethyl-3-phenyl-N-(3-phenylpropyl) propan-1-amine, commonly used as a smooth muscle relaxant, antispasmodic in irritable bowel syndrome and dysmenorrheal agent. A simple and sensitive Infrared spectrophotometric method has been developed for the estimation of alverine citrate in capsule dosage form. The Method involves the determination of alverine citrate by absorbance and peak area method of IR spectrophotometry. The sample was analyzed by KBr pellet method; IR band at 2052cm-1 was considered for quantification;. The calibration graph were plotted with a) absorbance against concentration b) area calculated by inbuilt software against concentration; The Beer’s law range was found to lie between 1-3mg. The correlation coefficient for the method was found to be 0.999 and the developed method was analyzed for specificity, limit of detection (LOD), limit of quantification (LOQ), linearity of response, precision and accuracy. Thus the proposed method could be adopted for routine analysis of bulk drug and its formulation.

 

 

 

INTRODUCTION:

Alverine is chemically N-ethyl-3-phenyl [-3-phenyl propyl]-1-propanamine, commonly used as a smooth muscle relaxant, anti-spasmodic in irritable bowel syndrome and dysmenorrheal agent1. Estimation of alverine citrate in bulk and formulation by IR Spectrophotometry has not been reported; hence the present work has been undertaken.

 

MATERIALS AND METHOD^{2, 3,and4}:

All the chemicals used throughout the experiment are of highest purity of IR grade.

1. Potassium bromide (KBr)

2. Internal standard: potassium thiocyanate

3. Chloroform

 

EXPERIMENTAL METHODS:

Instrumentation:

All spectral measurements were made on ABB-IR instrument (model no. MB 3000) with KBr press.

 

Preparation of standard:

25 mg of alverine citrate was weighed and transferred into 100 mL standard flask. Added 50 mL of chloroform  into the standard flask and shaken well, then made up to 100 mL .(0.25mg/ml) with chloroform. The volume containing  the required amount of drug was evaporated on a china dish.

To the dry residue a known quantity of KBr containing 0.2%w/w internal standard (Potassium thiocyanate) was added and ground in  an agate mortar and pestle. The KBr pellet made out of this mixture is used for IR quantification

 

Preparation of sample:

The average weight of 20 capsules of alverine citrate was determined and the contents were finely powdered. The powder equivalent to 25 mg of alverine citrate was taken in 100 mL volumetric flask, dissolved and volume made up with chloroform. The solution was filtered; first few mL of the filtrate was discarded. Aliquot quantity of filtrate is evaporated on a china dish to give the required amount of drug. To the dry residue a known quantity of KBr containing 0.2%w/w internal standard was added and ground in an agate mortar and pestle. The KBr pellet made out of this mixture is used for IR quantification

 

Experimental Procedure^3and4:

A known quantity of potassium thiocyanate makes an excellent internal standard. It was preground, dried, and then reground with dry KBr . The final mixture is stored over phosphorus pentoxide. A standard calibration curve is made by mixing known weights of the standard substance with a known weight of the KBr-KSCN mixture.

 

KBr/KCNS (in mg)	50	50	50	50	50	50
Standard (in mg)	0.0	1.0	1.5	2.0	2.5	3.0

 

Fig 1: Overlain Spectra of standard alverine citrate with internal standard (KBr/KSCN)

 

 

Calibration by using Absorbance:

Five discs were prepared by using KBr press and the infrared spectrum was recorded in an absorbance mode; the calibration curve was obtained by plotting   the IR absorbance at 2052 cm-1 (prominent band), against the concentration of the substance (Fig-1). The sample absorbance was interpolated on the respective linearity chart and the concentration was determined (Fig-2).

 

Fig 2 : Calibration graph of alverine citrate concentration  versus  absorbance.

 

Calibration using peak area:

In the similar way the calibration curve was constructed using peak area and concentration of the various standards (Fig-3). The sample absorbance was interpolated on the respective linearity chart and the concentration was determined (Fig-4).

 

 

RECOVERY STUDIES¹:

The recovery studies were carried out on spiked samples by adding predetermined amount of standard drugs to the respective sample.   The absorbance was measured.  The recovery study was performed at two levels to confirm the precision and accuracy of the above said method

 

RESULTS AND DISCUSSIONS:

Alverine citrate was found to obey Beer’s law in the concentration range of 1-3mg. Alverine citrate showed good linearity as indicated by correlation coefficient value of to 0.998. The optical parameters of alverine citrate are presented in table no.1. The percentage of the drug in the formulation was calculated and presented in table no.2.

 

Fig-3 IR Spectra of std alverine citrate with internal standard

 

Table 1: Optical parameters of alverine citrate by IR –spectroscopy

S.No	Parameters	Calibration by absorption	Calibration by area
1	Beer’s law limit(mg)	1-3mg	1-3mg
2	Regression equation( y= mx+c)	0.295x+0.171	19.853x-0.1564
3	Slope( m)	0.30	19.85
4	Intercept ( c )	0.02	-0.16
5	Correlation coefficient	0.998	.999
6	LOD (µg/mL)	8.69	7.68
7	LOQ (µg/mL )	26.34	23.26

*Each value is a mean of 3 determinations

 

Table 2: Assay and Recovery of Alverine citrate by IR Spectroscopy

S.No	Methods	Label claim(mg)	Amount of drug found(mg)	Amount of drug added(mg)	Amount of drug recovered(mg)	% Recovery
a	Calibration by  absorbance	60	60.8	30 60	29.64 61.2	99.1 101.9
b	Calibration  by  area		60.3	30 60	30.03 60.7	100.1 101.1

*Each value is a mean of 3 determinations

 

 

Fig-4 calibration graph of alverine citrate Concentration Vs area

 

The results of the analysis showed that the amount of drug present in the formulation was in good agreement with the label claim of the formulation. The accuracy of the proposed method was determined by recovery study. The recovery studies were carried out on spiked samples at two levels 50%, 100%. The percentages recovered were found to be in the range of 99-100% represented in table.2 which showed that the excipients in the formulation did not interfere with the analysis. The IR quantification process does not involve prior extraction and is independent of drug materials solubility.

 

CONCLUSION:

The percentage recovery of the method lies between 99-100 %. The correlation coefficient for the method was found to be 0.998 and the recovery studies indicates that there is no interference of other ingredients present in the formulation. Thus the method is simple, precise, accurate, less time consuming and could be used for routine analysis.

 

REFERENCES:

1.       Niraimathi V, Jerad Suresh A, Nanjappan K Spectrophotometric estimation of Nislodipine in bulk and tablet dosage formulation. Acta Ciencia Indica 2010; xxxvi C(4):393.

2.       Andreia de Haro Moreno, Herida Regina Nunes Salgado   Development and Validation of the Quantitative Analysis of Ceftazidime in Powder for Injection by  Infrared Spectroscopy  Physical Chemistry 2012,2(1):6-11

3.       Vogel’s  Textbook of Quantitative Chemical Analysis  by  J mendhan, Denney Thomas, Sixth Edition, New York , Pearson education publisher  p 734-74Pharmaceutical chemistry instrumental techniques  vol .2 by leslie G Chatten  P108-125

4.       Pharmaceutical chemistry instrumental techniques vol-2 by Leslieg.Chatten p108-125

5.        British Pharmacopeia,2009,Department of Health and Social services for Northern Ireland, Vol-I  and  Vol-III

 

 

Received on 18.01.2013       Modified on 10.02.2013

Accepted on 10.03.2013      © RJPT All right reserved