Estimation of Drotaverine hydrochloride by extractive colorimetric Methods in Bulk and Pharmaceutical Dosage Form
Rajan V. Rele*, Prathamesh P. Tiwatane
Central Research Laboratory, D.G. Ruparel College, Matunga, Mumbai 400016.
*Corresponding Author E-mail: drvinraj@gmail.com
ABSTRACT:
Simple sensitive and accurate extractive spectrophotometric methods have developed for the estimation of drotaverine hydrochloride in pharmaceutical dosage form. The methods are based on the formation of coloured complexes by the drug with reagents like bromophenol blue, solochrome dark blue and bromocresol green in acidic medium. The ion associated complexes were formed and quantitatively extracted under the experimental condition in chloroform. The absorbance values were measured at 420 nm, 495 nm and 430 nm respectively. The proposed methods were validated statistically. Recoveries of methods were carried out by standard addition methods. The linearity was found to be 1-9 μg/ml, 2 -16μg/ml, 1-16 μg/ ml for methods 1, 2 and 3 respectively. The low values of standard deviation and percentage RSD indicate high precision of methods. Hence these methods are useful for routine estimation of drotaverine hydrochloride in tablets.
Drotaverine hydrochloride is [(1-(3,4– diethoxybenzylidene)-6,7–diethoxy-1,2,3,4 tetrahydroiso quinoline) hydrochloride], a benzylisoquinoline derivative. It is a highly potent spasmolytic drug. It shows excellent properties of smooth muscle relaxant. Its antispasmodic activity is due to inhibition of phosphodiesterase enzyme IV. It causes smooth muscle relaxation by increasing intracellular levels of cyclic adenosine mono-phosphate (cAMP) secondary to inhibition of phosphodiesterase.
According to the literature review several methods has been developed for drug, like spectroscopy, methods1-9. HPLC10-14 and non aqueous titration15. The proposed aim of the study was to develop simple, accurate, specific and precise spectrophotometric method for the estimation of drug in the bulk and pharmaceutical formulation.
Structure of Drotaverine:
MATERIALS AND METHOD:
A Shimadzu -160 A double beam UV-Visible recording spectrophotometer with pair of 10mmmatched quartz cell was used to measure absorbance of solutions. A Shimadzu analytical balance was used.
Bromophenol blue, solochrome dark blue, bromocresol green, hydrochloric acid, potassium hydrogen phthalate and chloroform of A.R. grade were used in the study.
Preparation of standard solution and reagents
Stock solution of drotaverine hydrochloride (100 μg/ml) was prepared in distilled water. From this stock solution working standard (10 μg /ml) was prepared by diluting 10 ml stock solution to 100mlwith distilled water. 0.6%w/v solution of bromophenol blue, 0.25 %w/v solochrome dark blue and 0.2 %w/v bromocresol green were prepared in distilled water respectively.
Potassium hydrogen phthalate buffer solution of pH 4.01was prepared in distilled water. Dilute hydrochloric acid was used to adjust desired pH of buffer solution.
EXPERIMENTAL
Method 1 (with bromophenol blue)
Into a series of separating funnels appropriate amount of the working standard drug solutions were pipetted out. To each funnel 1.2 ml of buffer (pH= 4.1) and 6.2 ml of 0.6 %w/v bromophenol blue were added. 10 ml of chloroform was added to each funnel. The solutions were shaken for thorough mixing of the two phases and were allowed to stand for clear separation of the layers. The absorbance values of the chloroform layers were measured against their respective reagent blank at the wavelength of the maximum absorbance (λ max 420 nm).
Method 2 (with solochrome dark blue)
Into a series of separating funnels appropriate amount of the working standard drug solutions were pipetted out. To each funnel 4.5 ml of buffer (pH = 1.10) and 5 ml of 0.25% w/v solochrome dark blue were added. 10ml of chloroform was added to each funnel. The solutions were shaken for thorough mixing of the two phases and were allowed to stand for clear separation of the layers. The absorbance values of the chloroform layers were measured against their respective reagent blank at the wavelength of the maximum absorbance (λ max=495 nm).
Method 3 (with bromocresol green)
Into a series of separating funnels appropriate amount of the working standard drug solutions were pipetted out. To each funnel 1.1ml of buffer (pH= 3.7) and 4.2 ml of 0.02% w/v bromocresol green were added. 10 ml of chloroform was added to each funnel. The solutions were shaken for thorough mixing of the two phases and were allowed to stand for clear separation of the layers. The absorbance values of the chloroform layers were measured against their respective reagent blank at the wavelength of the maximum absorbance (λmax =430 nm).
Estimation from tablets
Twenty tablets were weighed accurately and average weight of each tablet was determined. Powder equivalent to 10 mg of drotaverine hydrochloride was weighed and transferred in 100 ml of volumetric flask. A 30 ml of distilled water was added and sonicated for 15 minutes and filtered. The filtrate and washing were diluted up to the mark with distilled water to give concentration as 100 μg /ml. Such solution was used for analysis.
Results of Analysis are given in Table 1.
Table 1: Values of results of optical and regression of drug
|
Parameter |
Bromo phenol blue |
Solo chrome dark blue |
Bromo cresol green |
|
Detection Wavelength (nm) |
420 |
495 |
430 |
|
Beer Law Limits (µg/ml) |
1-9 |
2-16 |
1-16 |
|
Correlation coefficient (r2) |
0.9999 |
0.9999 |
0.9999 |
|
Regression equation (y=b+ac) |
|||
|
Slope (a) |
0.0501 |
0.0201 |
0.035 |
|
Intercept (b) |
0.0012 |
0.0017 |
0.0021 |
RESULTS:
The extractive spectrophotometric methods are popular due to their sensitivity in assay of the drug and hence ion pair extractive spectrophotometric methods have gain considerable attention for quantitative determination of many pharmaceutical preparations. These proposed methods are extractive spectrophotometric methods for the determination of drotaverine hydrochloride by using chloroform as solvent from its formulations i.e. tablets. The colour ion pair complexes formed are very stable. The working conditions of these methods were established by varying one parameter at time and keeping the other parameters fixed by observing the effect produced on the absorbance of the colour species. The various parameters involved for maximum colour development for these methods were optimized. The proposed methods were validated statistically and by recovery studies. The molar absorptivity show the sensitivity of methods while the precision was confirmed by %RSD (relative standard deviation). The optical characteristics such as absorption maxima (nm), molar absorptivity (l -mole-1 cm-1), co-relation coefficient (r) were calculated and are also summarized. Assay results of recovery studies are given in table 2 (A,B,C).
Table no 2: A (Bromophenol blue
|
Amount of Sample Added in (µg/ml) |
Amount of Standard Added in (µg/ml) |
Total amount recovered |
Percentage recovery (%) |
Standard deviation |
Percentage of relative standard deviation (C.O.V.) |
|
1 |
0 |
1.002521 |
100.2521 |
0.001482 |
0.147849 |
|
2 |
1 |
2.008403 |
100.4202 |
0.019135 |
0.952762 |
|
3 |
2 |
3.002801 |
100.0934 |
0.030855 |
1.027532 |
|
4 |
3 |
4.002801 |
100.07 |
0.020962 |
0.523675 |
|
|
|
|
|
Mean= 0.018108 |
Mean= 0.662954 |
Table no 2: B (Solochrome dark blue)
|
Amount of Sample Added in (µg/ml) |
Amount of Standard Added in (µg/ml) |
Total amount recovered |
Percentage recovery (%) |
Standard deviation |
Percentage of relative standard deviation (C.O.V.) |
|
2 |
0 |
2.014634 |
100.7317 |
0.008906 |
0.442068 |
|
2 |
2 |
4.020906 |
100.5226 |
0.047605 |
1.183934 |
|
2 |
4 |
6.020906 |
100.3484 |
0.088422 |
1.468585 |
|
2 |
6 |
8.020906 |
100.2613 |
0.062069 |
0.773842 |
|
|
|
|
|
Mean= 0.051751 |
Mean= 0.967108 |
Table no 2:C (Bromocresol green)
|
Amount of Sample Added in (µg/ml) |
Amount of Standard Added in (µg/ml) |
Total amount recovered |
Percentage recovery (%) |
Standard deviation |
Percentage of relative standard deviation (C.O.V.) |
|
2 |
0 |
2.003622 |
100.1811 |
0.002129 |
0.106276 |
|
2 |
2 |
4.012475 |
100.3119 |
0.026317 |
0.65589 |
|
2 |
4 |
6.028169 |
100.4695 |
0.032527 |
0.53958 |
|
2 |
6 |
8.012072 |
100.1509 |
0.045587 |
0.568982 |
|
|
|
|
|
Mean= 0.02664 |
Mean= 0.467682 |
Results are in good in agreement with labelled value.
DISCUSSION:
The percent recovery obtained indicates non interference from the common excipients used in the formulation. The reproducibility, repeatability and accuracy of these methods were found to be good, which is evidenced by low standard deviation. The proposed methods are simple, sensitive, accurate, precise and reproducible. They are directly applied to drug to form chromogen. Hence they can be successfully applied for the routine estimation of drug, in bulk and pharmaceutical dosage form even at very low concentration and determination of stability of drug in formulation such as tablets. The strong recommendation is made here for the proposed methods for determination of drotaverine hydrochloride from its formulation.
ACKNOWLEDGMENT:
Authors express sincere thanks to the Principal, of D. G. Ruparel College
REFERENCES:
1. Tulja rani G, Gowri Sankar D, Kadgapathi P, Suthakaran R. and Satyanarayana B., Visible Spectrophotometric Methods for the Determination of drotaverine Hydrochloride in Bulk and in Pharmaceutical Formulations. International Journal of Pharm Tech Research. 2010; 2(3): 1787-1791.
2. Rajan Rele. UV spectrophotometric estimation of drotaverine hydrochloride by zero order and area under curve methods in bulk and pharmaceutical dosage form. Research J. Pharm. and Tech. 2018; 11(12): 5576-5580. DOI: 10.5958/0974-360X.2018.01014.4
3. Rajan Rele. UV- spectrophotometric estimation of drotaverine hydrochloride by derivative method in pharmaceutical dosage form. International Journal of Chem Tech Research. 2018; 11(10): 353-360.
4. Syeda Sheeba Ahamadi, Karuppa Samy. C, Syeda Bushra Yunus, Nagaraju. C, Dilip Kumar. P1, Madhu Kumar. G., Method development and validation of spectrophotometric method for the estimation of drotaverine hydrochloride in bulk and tablet dosage form. Asian Journal of Pharmaceutical Analysis and Medicinal Chemistry. 2013; 2(1): 110-117.
5. S. A. Shah, D. R. Shah, R. S. Chauhan and J. R. Jain, Development and Validation of Simultaneous spectrophotometric Methods for drotaverine Hydrochloride and Aceclofenac from Tablet Dosage Form. Indian Journal of Pharmaceutical Sciences. 2011; 73(3): 296-300.
6. Ram Babu Durgam, Sireesha, V.V.L.N Prasad, Prakash V Diwan. Analytical method development and validation of drotaverine hydrochloride and aceclofenac in bulk and pharmaceutical dosage forms by UV-Spectrophotometer. International Journal of Drug Development and Research. 2013; 5(4): 268-272.
7. Prabhu Padmavathi P, Paramita Das, Panara Krunal, E.V.S. Subrahmanyam. Analytical method development and validation for estimation of drotaverine hydrochloride in bulk and tablet formulation. Asian Journal of Biomedical and Pharmaceutical Sciences. 2013; 3(22): 75-78.
8. Alla Yegorova, et al. Determination of drotaverine hydrochloride in dosage forms by its quenching effect on the luminescence of terbium complex. Journal of Applied Pharmaceutical Science. 2018; 3(5): 6-11.
9. Smita Sharma, Mukesh C. Sharma. Development and validation of new analytical methods for simultaneous estimation of drotaverine hydrochloride in combination with Omeprazole in a pharmaceutical dosage form. Arabian Journal of Chemistry. 2017; 10(s): 397-403.
10. B. S. Sastry, S. Gananadhamu_ and G. Devala Rao. Development of RP-HPLC method for estimation of drotaverine hydrochloride in pharmaceutical formulations. International Journal of Chemical Sciences. 2008; 6(4): 2055-2061.
11. P. Balan, I. Carolin Nimila, Sasirekha Chundi, Vanaja Rani Movva, S. Rajasekar. A validated RP-HPLC method for estimation of drotaverine hydrochloride in pharmaceutical tablet dosage form. International Journal of Pharmaceutical Sci, 2011; 3(4): 77-80.
12. D. Snigdha. Development and validation of stability indicating RP-HPLC method for the determination of drotaverine hydrochloride: International. Journal of Pharm Drug Anal. 3(7): 234- 245.
13. Rele Rajan V. Development and validation of analytical method by RP-HPLC technique for determination of drotaverine hydrochloride in pharmaceutical dosage form. International Journal of ChemTech Research. 2017; 10(100): 77-84.
14. Rele Rajan V. Reverse phase high performance liquid chromatography for simultaneous validation of aceclofenac and drotaverine hydrochloride bulk and pharmaceutical dosage form. International Journal of ChemTech Research. 2017; 10(13): 266-272.
15. Rajan Rele. A Non-Aqueous Potentiometric Titration Method for Validation of drotaverine Hydrochloride from Pharmaceutical Dosages. International Journal of ChemTech Research. 2018; 11(11): 226-231.
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Received on 07.03.2025 Revised on 22.04.2025 Accepted on 29.05.2025 Published on 12.08.2025 Available online from August 18, 2025 Asian J. Research Chem.2025; 18(4):213-216. DOI: 10.52711/0974-4150.2025.00033 ©A and V Publications All Right Reserved
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