Absorbances Ratio Method (Isoabsorptive Point) for Determination of Drotaverine Hydrochloride and Ranitidine Hydrochloride from Pharmaceutical Dosage Forms

 

Khandelwal Pankaj1*, Shrivastava B.S.2, Goyal Anju3

1Department of Quality Assurance, Mahatma Gandhi College of Pharmaceutical Sciences,

Sitapura, Jaipur (Rajasthan) INDIA-302022

2School of Pharmaceutical Sciences, Jaipur National University, Jaipur, Rajasthan, INDIA

3Department of Pharm. Chemistry, B.N. Girls College, Udaipur, Rajasthan, INDIA

*Corresponding Author E-mail: khandelwalpankaj09@gmail.com

 

ABSTRACT:

A simple, reproducible and efficient method for the simultaneous determination of drotaverine hydrochloride and ranitidine in pharmaceutical dosage form was developed. Drotaverine hydrochloride and ranitidine in combination are available as tablet dosage forms in the ratio of 1:3.75. The proposed method is based on the Absorbances ratio method. From overlain of absorption spectra, wavelength 324.4 nm ((isoabsorptive point)) and 351.4 nm were selected for the construction of absorbance ratio equation. The linearity was observed in the concentration range of 2-60 µg/ml for drotaverine hydrochloride and 2-32 µg/ml for ranitidine at given wavelengths. Both the drugs obey Beer’s law. The method was validated as per ICH guidelines. The recovery studies confirmed the accuracy of the proposed methods.

 

KEYWORDS: Drotaverine hydrochloride, Ranitidine hydrochloride, spectrophotometry, Absorbances Ratio Method, Validation.

 

 

INTRODUCTION:

Drotaverine hydrochloride, chemically 1-[(3,4-Diethoxyphenyl) methylene]-6,7- diethoxy1, 2,3,4-tetrahydroisoquinoline hydrochloride, is an isoquinoline derivative is used as an antispasmodic agent which act by inhibiting phosphodiesterase IV enzyme, specific for smooth muscles spasm and pain mainly labor pain1, 2. It is not official in any pharmacopoeia. Only HPLC methods have been developed for determination of drotaverine hydrochloride in human plasma and urine3, 4.

 

Ranitidine, chemically Dimethyl {5-[2-(1-methylamino-2-nitrovinyl amino) ethylthiomethyl] furfuryl}-amine hydrochloride, used as histamine H2-receptor antagonist that inhibits stomach acid production, and commonly used in the treatment of peptic ulcer disease (PUD) and Gastroesophageal reflux disease (GERD) 5,6. Ranitidine is official in IP, BP and USP, and it is assayed by HPLC method.

 

The extensive literature survey reveals that numbers of methods are reported for the individual drugs but no method is so far reported for the simultaneous estimation of both the drugs in combined pharmaceutical dosage form. Therefore, we attempted to develop a simple and efficient spectrophotometric method for simultaneous estimation of drotaverine hydrochloride and ranitidine in combined dosage form7, 8.

 

EXPERIMENTAL:

Instrument:

1)    UV-VIS Spectrophotometer (Elico SL 160).

a)     Spectral bandwidth of 1.8 nm.

b)    Wavelength accuracy of 0.5 nm.

(2)   Matched quartz cells of 10 mm optical path length.

 

Solvent: Distilled water

 

Preparation of standard solution:

10 mg drotaverine hydrochloride was accurately weighed, dissolved in double distilled water in a 100 ml volumetric flask and then volume was adjusted to 100 ml with double distilled water to obtain stock solution of drug of concentration of 100 µg/ml. Working standard solutions of drotaverine hydrochloride were prepared by diluting different volumes of stock solution (100 µg/ml) in a 10 ml volumetric flask to give a concentration range of 2 to 60 µg/ml using double distilled water.

 

11.2 mg ranitidine hydrochloride (1.12 g ranitidine hydrochloride equivalent to 1.0 g ranitidine) was accurately weighed, dissolved in double distilled water in a 100 ml volumetric flask and then volume was adjusted to 100 ml with distilled water to obtain stock solution of drug of concentration of 100 µg/ml. Working standard solutions of ranitidine were prepared by diluting different volumes of stock solution (100 µg/ml) in a 10 ml volumetric flask to give a concentration range of 2 to 32 µg/ml using distilled water.

 

Development of simultaneous equations for determination of drotaverine hydrochloride and ranitidine:

Two equations were constructed and concentrations of ranitidine and drotaverine hydrochloride in the sample mixture can be calculated by using equation 1 and 2, respectively9, 10.

 

CRANITIDINE= {(1.489-Q1) X A1 X 1000} / 58.436             (1)

 

CDROTAVERINE={(Q1-0.091) X A1 X 1000}/ 19.991…        (2)

 

Where, CRANITIDINE and CDROTAVERINE are the concentration of ranitidine and drotaverine, respectively, A1 is the absorbance of sample at 324.4 nm and value of Q1 obtained from, (absorbance of sample at 351.4 nm)/ (absorbance of sample at 324.4 nm).

 

Selection of analytical wavelengths was done by taking overlain spectra of both the drug samples of drotaverine hydrochloride and ranitidine (Fig.1). The overlain spectra show that peaks are well resolved thus satisfying criteria for obtaining maximum precision based on absorbances ratios and wavelength 324.4 nm and 351.4 nm (λmax of ranitidine and drotaverine, respectively) were selected for the formation of simultaneous equations.

 

Figure.1 Overlain of absorption spectra of drotaverine hydrochloride (25 µg/ml) and ranitidine (10 µg/ml).

 

Figure 2: Calibration Curve for Drotaverine Hydrochloride at 324.4 nm

 

Figure 3: Calibration Curve for Ranitidine at 324.4 nm

 

Calibration curves of drotaverine hydrochloride and ranitidine were plotted at both the selected wavelengths using appropriate dilutions of stock solutions respectively in distilled water (Fig.2 and Fig.3).

 

Drotaverine hydrochloride and ranitidine showed linearity individually in the range of 2-60 µg/ml and 2-32 µg/ml respectively. The absorptivities of both drugs at both drugs at both the wavelength were determined (Table-1).

 

 

 

 

TABLE 1: Optical and Regression Characteristics of Drotaverine Hcl and Ranitidine HCl:

Parameters

Drotaverine Hydrochloride

Ranitidine

λmax

351.4 nm

324.4 nm

351.4 nm

324.4 nm

Regression equationa

y=0.0213x+0.0061

y=0.0143x-0.0043

y=0.0038x-0.004

y=0.0418x+0.0019

Slope (b)

21.3x10-3

14.3x10-3

3.8 x10-3

41.8x10-3

Intercept (a)

6.1x10-3

4.3x10-3

4x10-3

1.9x10-3

Linearity range (mg/ml)

2-55

2-60

2-32

2-32

Molar absorptivity (Lit/mole/cm)

9.072x103

6.09x103

1.194x103

1.314*104

Correlation Coefficient (r)

0.9997

0.9995

0.9982

0.9998

  a means y=a+bC

 

Preparation of sample solution:

Marketed formulation (Ranispas DV from Mankind Pharmaceuticals) contains ranitidine hydrochloride equivalent to 150 mg of ranitidine and 40 mg of drotaverine hydrochloride in a tablet dosage form. The contents of 20 tablets were weighed accurately and mixed uniformly. An accurately weighed quantity of powder equivalent to 150 mg of ranitidine and 40 mg of drotaverine hydrochloride was taken into a 100 ml volumetric flask and sufficient quantity of distilled water was added to it. It was then sonicated for about 15 min and the volume made up with distilled water. It was filtered and the filtrate diluted to get a suitable concentration. The assay was carried out and the results are shown in (Table 2).

 

TABLE 2: Assay of marketed formulation:

 

Ranispas DV Tabs.

Drotaverine HCl

Ranitidine HCl

Label claim (mg/tab)

40

150

% Drug content *

101.35

98.78

% RSD

1.11

0.30

* Average of five readings

 

VALIDATION OF PROPOSED METHOD:

Linearity study:

Calibration curves of drotaverine hydrochloride and ranitidine were plotted at both the selected wavelengths using appropriate dilutions of stock solutions respectively in distilled water. Drotaverine hydrochloride and ranitidine showed linearity individually in the range of 2-60 µg/ml and 2-32 µg/ml respectively. High value of the correlation coefficient indicates good linearity and adherence of the method to Beer’s law (Table 1).

 

Recovery studies:

To study validity and reproducibility of the proposed method, recovery studies were carried out by adding a known amount of drug to preanalysed sample at three different levels and the percentage recoveries were calculated. Percent recovery of both the drugs was found to be within limits.

 

Repeatability:

Repeatability is performed by intra - and inter - day precision. Intra-day precision was determined by analyzing the three different concentrations of drug for three times in the same day. Inter-day precision was determined by analyzing the three different concentrations of the drug for three days in a week. The precision of the assay for drotaverine hydrochloride and ranitidine hydrochloride was determined and found to be lower than 0.51 % and 1.7 %, respectively.

 

RESULTS AND DISCUSSION:

A simultaneous equation method was successfully developed for the simultaneous determination of drotaverine hydrochloride and ranitidine in combined dosage form. The method for both the drug at the selected wavelengths was found to be precise and accurate as indicated by interday and intraday analysis, showing percent relative standard deviation (% RSD) less than 2. Marketed tablets were analyzed and amount of drug was determined by proposed method; it was in good agreement with the label claim. Recovery studies of the drugs were carried out at three levels 80,100 and 120% and the recovery ranges from 98.38-100.66% for drotaverine hydrochloride and 98.56-101.19% for ranitidine hydrochloride, which shows the accuracy of method. Thus develop method is simple, accurate, precise, and economical and can be used for routine analysis of drotaverine hydrochloride and ranitidine simultaneously from a combined dosage from a combined dosage form.

 

ACKNOWLEDGEMENTS:

The authors are thankful to Jagsonpal Pharmaceutical, New Delhi and Monarch Pharma, Chandigarh for providing the gift samples of the drug.

 

REFERENCES:

1.      J Maryadele, J.O., Neil, A. S., The Merck Index (30th ed.), Merck Research Laboratories, NJ, USA, 2001, 3489

2.       Singh K.C., Jain P., Goel N. and Saxena A., Drotaverine hydrochloride for augmentation of labor, Inter. J. Gyneco. and Obst.2004, 84(1), 17-21

3.       Fadia, H., Metwally, Journal of AOAC International Vol. 89; 1 Jan-Feb 2006, 78-87.

4.       El-Saharty, Y.S., Metwaly FH, Refaat, M., El-Khateeb, SZJ., Pharm Biomed Anal. 2006 Feb 7

5.       Maryadele, J.O., Neil, A. S., The Merck Index (30th ed.), Merck Research Laboratories, NJ, USA, 2001, 8198

6.       Martindale, The Extra Pharmacopoeia (30th ed.), The Pharmaceutical Press, London, 1993, 901.

7.       Hohnjec, M., Kuftinec, J., et al, Analytical Profile of Drug Substances, Ranitidine, Elsvier India Pvt. Ltd. New Delhi; Vol. 15, 533.

8.       British Pharmacopoeia 2004, Vol. II, 1683

9.       Beckett AH, Stenlake JB, Practical Pharmaceutical Chemistry. 4th ed. New Delhi: CBS Publishers and Distributors: 275-337.

10.    Skoog DA, Holler FJ, Nieman DA. Introduction to UV Spectroscopy In, Principle of Instrumental Analysis. 5th ed. Thomson Brooks/Cole publication. 2004; 1-4, 301.

 

 

 

Received on 18.04.2014       Accepted on 26.06.2014     

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Asian J. Pharm. Ana. 4(3): July-Sept. 2014; Page 113-115