About Author: Ashish Kumar Verma1, D.Raj. Anand1, Garima A. Tewari2
1. Jubilant Chemsys Limited Noida 201301
2. Babu Banarsi Das University Lucknow
ABSTRACT
Aceclofenac and paracetamol in combination are available as tablet dosage forms in the ratio of 1:5. A simple, reproducible and efficient method for the simultaneous determination of aceclofenac and paracetamol in synthetic mixture was developed. The proposed method is based on the Q-analysis UV Spectrophotometric method. The absorbance maxima of aceclofenac and paracetamol were found to be 275.4 nm and 248 nm, respectively in methanol. In Q-analysis, the isoabsorptive point for both the drugs was found at 266.1 nm. The linearity range lies between 1-35 µg/ml for aceclofenac and 1-15 µg/ml for paracetamol at their respective wavelengths. Both the drugs obey Beer’s law. The recovery studies confirmed the accuracy of the proposed methods.
Reference Id: PHARMATUTOR-ART-1163
INTRODUTION
Aceclofenac (ACL), chemically 2-[[2-[2-[(2,6 dichlorophenyl) amino] phenyl] acetyl] oxy] acetic acid is a new potent non-steroidal anti-inflammatory and analgesic drug of phenyl acetic acid group used in the treatment of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis with better gastric tolerance1. It is a new drug and find place in Martindale-Extra Pharmacopoeia2, Merck index3, European Pharmacopoeia4 and British Pharmacopoeia5. Few methods such as titrimetric4,5, stripping voltammetric6, spectrophotometric and spectroflourimeteric7, and high performance liquid chromatographic (HPLC)8,9 have been reported for its estimation.
Paracetamol (PCM), chemically N- (4- hydroxy phenyl) acetamide is a salicylate like non-steroidal anti-inflammatory drug that has analgesic and antipyretic properties. It is official in IP10, BP5, and USP11.
Both these drugs are available in combined tablet dosage form (100 mg aceclofenac and 500 mg paracetamol) as an antirheumatoid.
The extensive literature survey reveals that number 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 dosage form. So, the attempts have been made to develop a simple, sensitive and reproducible Q-analysis12 method for the simultaneous estimation of aceclofenac and paracetamol in synthetic mixture
MATERIALS AND METHODS (EXPERIMENTAL)
Instrument –
(1) Elico SL 160 Double beam UV-VIS Spectrophotometer.
a) Spectral bandwidth of 1.8 nm.
b) Wavelength accuracy of 2 nm.
c) Matched quartz cells of 10 mm optical path length.
(2) GR 200 Analytical weighing balance (AND company).
(3) Sonicator (Enertech Electronics).
Reagents – Methanol A.R. Grade (Loba Chemie, New Delhi)
Drug samples – Aceclofenac and Paracetamol (Ipca Laboratories Ltd., Sejavta, Ratlam).
Procedure
Aceclofenac (10 mg) and paracetamol (10 mg) were accurately weighed and dissolved in methanol to give stock solution having concentration of 100 μg/ml. From these stock solutions, working standard solutions of drugs (10 μg/ml) was prepared by appropriate dilutions. Working standard solutions were scanned in the entire UV range to determine the λ-max. The λ-max of aceclofenac and paracetamol were found to be 275.4 nm and 248.0 nm respectively. Now for study according to Q-analysis method, standard solutions were prepared having concentrations 5, 8, 11, 14, and 17 μg/ml for aceclofenac and 5, 7, 9, 11 and 13 μg/ml for paracetamol using the working standard solution and absorbance values were taken at 266.1 nm from the overlain spectra of both the drugs.
Drug concentrations of 2 mg/ml (paracetamol), 10 mg/ml (aceclofenac) and a synthetic mixture containing the same concentration of both the drugs were analyzed.
The synthetic mixture of aceclofenac and paracetamol was prepared in ratio of 1:5. Accurately weighed 10 mg of aceclofenac (~ 50 mg of paracetamol) was transferred to 100 ml volumetric flask, and made-up the volume to 50 ml with methanol. Common excipients, which are used in tablet formulation, were added in this mixture and sonicatad for 20 minutes. This solution was filtered through the Whatmann filter paper No. 41 and residues were washed with methanol. The filtrate and washings were combined and diluted to the 100 ml with methanol. The decision of this ratio of drugs in the synthetic mixture was based upon the dosage strength of combination, which is available in the market. Aliquots of this synthetic mixture solution were diluted with methanol to get the working standards of 2 µg/ml aceclofenac (~ 10 µg/ml paracetamol). Absorbance of the synthetic mixture solutions were measured at 275.4 nm and 266.1 nm (iso-absorptive point) and from the absorbance values, the concentration of drugs in the synthetic mixture solution was determined by Q-analysis method.
TABLE 1: The absorptivity values of aceclofenac and paracetamol in the proposed methods.
|
Drug Name |
|
Absorptivity values* at (266.1 nm) |
|
ACL |
a1 |
28.76 |
|
PCM |
a2 |
31.48 |
- a1 and a2 are the absorptivity values of aceclofenac and paracetamol at isoabsorptive point.
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For estimating the concentration of aceclofenac and paracetamol by Q-analysis method, the absorbance and the absorptivity values at the particular wavelengths were calculated and substituted in the following equation: CX = (Q0 – Q2) x A1 / (Q1 – Q2) x a1, CY = (Q0 – Q1) x A1 / (Q2 – Q1) x a2, where CX and CY are concentration of aceclofenac and paracetamol, respectively. A1 is the absorbance of synthetic mixture at 266.1 nm, a1 and a2 are the absorptivity values of aceclofenac and paracetamol at 266.1 nm, respectively, Q0 was obtained by using the equation, (absorbance of synthetic mixture at 275.4 nm) / (absorbance of synthetic mixture at 266.1 nm), Q1 was obtained from (absorbance of aceclofenac at 275.4 nm) / (absorbance of aceclofenac at 266.1 nm), and Q2 was obtained from (absorbance of paracetamol at 275.4 nm) / (absorbance of paracetamol at 266.1 nm). The absorptivity values of aceclofenac and paracetamol at various wavelengths are given in Table 1.
TABLE 2: Regression analysis of calibration curves and summary of validation parameters.
|
Parameters |
ACL |
PCM |
ACL |
PCM |
|
Wavelength (nm) |
275.4 |
266.1 |
266.1 |
248 |
|
Beer’s law limit (µg/ml) |
1-35 |
1-14 |
1-35 |
1-14 |
|
Molar absorptivity (l mole-1cm-1) |
1.0 X 104 |
4.7 X 103 |
1.0 X 104 |
1.1 X 104 |
|
Limit of detection (µg/ml) |
0.1 |
0.5 |
0.1 |
0.5 |
|
Limit of quantification (µg/ml) |
0.5 |
0.8 |
0.5 |
0.8 |
|
Sandell's sensitivity (mg/cm2/. 001absorbance unit) |
0.03509 |
0.03674 |
0.03483 |
0.01265 |
|
Regression equation* |
|
|
|
|
|
Intercept (α) |
- 0.0055 |
0.0392 |
0.0392 |
- 0.0198 |
|
Slope (β) |
0.03 |
0.0243 |
0.0251 |
0.0815 |
|
Correlation coefficient (r2) |
0.9998 |
0.9989 |
0.9998 |
0.9984 |
Where, *Y= α + βx, x is the concentration of analyte and Y is the absorbance value.
TABLE 3: Assay and Recovery Studies Results of Aceclofenac and Paracetamol in the Synthetic Mixture
Drug |
Synthetic |
Standard |
Amount |
% Recovery |
Avg. Recovery ±S.D. |
|
|
ACL
|
2.00 |
1 |
2.966 |
99.13 |
99.71 ±0.520
|
|
|
2.00 |
1.5 |
3.481 |
99.86 |
|||
|
2.00 |
2 |
4.004 |
99.50 |
|||
|
2.00 |
2.5 |
4.498 |
100.35 |
|||
|
|
||||||
|
PCM
|
10.00 |
5 |
14.998 |
99.72 |
100.01 ±0.255
|
|
|
10.00 |
7.5 |
17.554 |
100.32 |
|||
|
10.00 |
10 |
20.062 |
100.10 |
|||
|
10.00 |
12.5 |
22.397 |
99.92 |
|||
* All the values are mean of five readings.
To study the linearity, accuracy and precision of the proposed method, the recovery studies were carried out by adding a known quantity of standard to the pre analyzed sample and the % recovery was calculated and shown in Table 3. The regression analysis of the calibration curves and the optical characteristics such as Beer’s law limits, detection limit, molar absorptivities and Sandell’s sensitivities are presented in Table 2.
Thus, the proposed method for simultaneous estimation of aceclofenac and paracetamol in synthetic mixture was found to be simple, accurate, sensitive and economical. Therefore, the method can be useful in routine equality quality control analysis.
REFERENCES
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4) European Pharmacopoeia (4th ed.), Council of Europe, Strasbourg cedex, France, 2002, 1281.
5) British Pharmacopoeia (4th ed.), vol.- 1, Her Majesty’s Stationary Office, London,UK, 2004, 36-38 and 1479-1481.
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8) L.Q. Gao, W.Y. Liu, J.D. Xing, Yaowu Fenixi Zazhi, 18(4) (1998), 219-222.
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10) Indian Pharmacopoeia, 1996 (4th ed.), vol.-2, Govt. of India, Ministry of Health and Family Welfare, Controller of Publications, New Delhi, 554.
11) United States Pharmacopoeia/NF, 2003. Asian ed., The Official Compendia of Standards, 16-19.
12) A.G. Davidson, A.H. Beckett, J.B. Stanlake, 2002 (4th ed.), vol.-2, Practical pharmaceutical chemistry, CBS Publishers and Distributors, New Delhi, 284
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