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Pakistan Journal of Pharmaceutical Sciences Vol. 18, No.4, October 2005, pp.1-
SPECTROPHOTOMETRIC METHODS FOR THE DETERMINATION
OF IBUPROFEN IN TABLETS
ABDEL AZIZ WAHBI, EKRAM HASSAN, DALIA HAMDY, ESSAM KHAMIS
AND MAGDA BARARY
Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, University of Alexandria, Alexandria 21521, Egypt E-mail: [email protected], +2034871317, +
Ibuprofen in film coated tablets of different strengths has been determined using different spectrophotometric methods. These are: (i) the compensation method, (ii) a two wavelengths method, (iii) second-order and (iv) fourth- order derivative methods, and (v) a curve fitting method based upon computing the quadratic coefficient of the orthogonal polynomials expansion of its benzenoid absorption characteristics. All results were compared with the HPLC method of the B.P. 2003 using paired comparison. Developed methods have been validated and applied to different tablet formulations. Mean differences from the B.P. method were found to be -0.10, -0.30, -0.10, -0.16, -0.34 %, respectively. In view of the relatively low specific absorbance of ibuprofen in the ultraviolet region [A (1%, 1cm) =18.5 at 264 nm] its accurate and precise determination in different tablet formulations is challenging due to the presence of interferences from excipients.
Keywords : Ibuprofen, NSAID, derivative spectrophotometry, tablets, curve fitting, compensation method, chemometrics.
INTRODUCTION
COOH
H 3 C
CH 3
CH 3
Ibuprofen (±)-2-(4-isobutylphenyl)propionic acid C 13 H 18 O (^2) Mol. wt. 206.
Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID). Although its anti-inflammatory properties may be weaker than those of some other NSAIDs, it has a prominent analgesic and antipyretic role. Its effect is due to its inhibitory action on cyclo-oxygenases which are involved in the biosynthesis of prostaglandins. Prosta- glandins have an important role in the production of pain, inflammation and fever. Its main adverse effects are gastro- intestinal disturbances.
Ibuprofen is official in the B.P. 2003 and the U.S.P. 27 NF
The U.S.P. method for the determination of ibuprofen and its tablets is by HPLC, using chloroacetic acid/acetonitrile as mobile phase, L1 column, valerophenone solution as an internal standard and a flow rate 2 ml/min and measuring response at 254 nm. A titrimetric method for ibuprofen determination and an HPLC method for the tablets using methanol/H 2 O/o-phosphoric acid as mobile phase, C
column, flow rate is 1.5 ml/min and detection wavelength of 264 nm are recommended by the B.P. 2003. Spectro- photometric methods for the determination of ibuprofen have also been published. A mixture of ibuprofen and methocarbamol has been determined in tablets using two wavelengths method (Satheesh-Manikandan et al., 2001).
First derivative spectrophotometry has been applied to the determination of mixtures of ibuprofen and dextro- propoxyphene (Sachan and Trivedi, 1998) and paracetamol (Basu et al., 1998) in solid dosage forms. Ibuprofen has also been determined in tablets through its copper complex (El- Raghy et al., 1994).
EXPERIMENTAL
Materials Ibuprofen (B.P. 2003) supplied from SPIMACO,( Qassim, Saudi Arabia), brufen tablets 200 mg (Knoll AG., Ludweghaven, Germany), ultrafen tablets 200mg, 400 mg, 600 mg (Glaxo Wellcome, Egypt), sabofen tablets 600 mg (SPIMACO).
Solvent The solvent was prepared from a mixture of 3 volumes orthophosphoric acid: 247 volumes of water: 750 volumes of methanol.
Apparatus A Perkin Elmer Lambda EZ201 UV/Vis spectrophotometer with 1-cm quartz cuvettes. The device is connected to a panasonic impact dot matrix printer 24 pin KX-P 3626.
2 Spectrophotometric methods for the determination of ibuprofen in tablets
Standard solution Ibuprofen standard solution (2.0 mg/ml) was prepared in the above mentioned solvent.
For HPLC measurements: the stock solution was injected into a C18 column at flow rate of 1.5 ml/min at ambient temperature. A volume of 1.00μL was injected and detected at 264 nm.
For UV measurements: aliquot volumes of 4 to 14ml (in 2- ml steps) of standard ibuprofen solution were transferred into 100-ml calibrated flasks and diluted to volume with the same solvent to contain final concentrations of 80 to 280 μg/ml, respectively. Absorption curves were recorded over the wavelength range 220-300nm at 2-nm intervals at scan speed 100 nm/min.
Procedures Ten ibuprofen tablets of each product were accurately weighed, ground and mixed well. A quantity of the resulted powder equivalent to about 200 mg ibuprofen was accurately weighed and transferred into 100-ml calibrated flasks using the prepared solvent. The flasks were sonicated for 30 minutes and dilutions were completed to volume. The tablets extracts were then centrifugated at 2500 rpm for 5 min.
For HPLC measurements: the centrifugate was injected into a C18 column at a flow rate of 1.5 ml/min and detection wavelength of 264 nm.
For UV measurements: aliquot volumes of 4 to 14ml (in 2- ml step) of stock solutions were transferred into 100-ml calibrated flasks and diluted to volume with the same solvent to contain final concentrations of 80 to 280 μg/ml. The absorbance (zero-order) and the absorbance difference of sample vs. reference (compensation method) were recorded for each solution at 2-nm intervals over the wavelength range 220-300nm at scan speed 100 nm/min.
RESULTS AND DISCUSSION
Application of the compensation method The compensation method is a non-mathematical method, which despite the need for personal judgment, is very useful in practice. The irrelevant absorption curve is assumed to possess the simplest possible shape and none of the characteristics of the pure compound.
The compensation method involves a comparison of several difference spectra, (sample-reference) using different concentrations of reference substance in the reference cell. Thus, if A (^) s and Ar refer to the absorbance of the relevant cells against air for sample and reference,
∆A = A (^) s - A (^) r (1)
The pure compound characteristic peak, which may be seen in the ∆A curve, gradually diminishes as Cr increases, finally disappearing at the balance point, for which Cr = Cs. Further increase in Cr then leads to an over-compensated difference curve which bears an inversion of the pure compound’s characteristic peak (figure 1). The difference curve at the balance point coincides with the irrelevant absorption present. The accuracy of the method in the assay of single and multi-component mixtures depends upon correct evaluation of the balance point. The method has been successfully applied to the determination of single component in the presence of interference arising from either additives or degradation products. The compensation method has been computerized (Wahbi et al., 1989) to facilitate its application.
Ibuprofen has been determined in tablets using the compensation method. The method has also been used to reveal the presence and shape of irrelevant absorption due to tablet excipients. The latter has been detected at the balance point. Table 1 shows the results obtained for the deter- mination of ibuprofen in five tablet formulations using the compensation method. In all cases the results obtained were found to be within ±5% of the labeled quantity and therefore
Fig. 1: Application of the compensation method to the determination of ibuprofen in product C, (Ultrafen 400 mg) tablets., (a) gross curve, (b) and (C) difference curves obtained by compensation, (Z) the balance point = irrelevant absorption curve, (d) and (e) over compensated curves.
4 Spectrophotometric methods for the determination of ibuprofen in tablets
The absorbance difference at two wavelengths has been applied to the determination of ibuprofen in tablets. The maximum wavelength at 264 nm was selected and the second wavelength was 280 nm, where ibuprofen showed negligibly low absorbance contribution. The results obtained are shown in table 1. The mg of ibuprofen per tablet was found to be within ±5% of the labeled amount. This complies with both the B.P. and the USP specifications for ibuprofen in tablets.
Fig. 2(a) Absorption curve of 200μg / ml of ibuprofen in the solvent, its D 2 (b) and D 4 (c) derivative curves.
Specificity The absorption characteristics of the tablet solution with two maxima at 264 nm and 272 nm and a shoulder at 258 nm together with the compensation method explain the specificity of the method.
Linearity range The absorbance difference at A (^) 264nm-A (^) 280nm for ibuprofen in the solvent used was found to be linearly related to concentration over the range 80 to 280 μg/ml. The regression analysis of the linear relationship is shown in table 2.
Application of derivative spectrophotometry Second and fourth order derivative curves of ibuprofen have been recorded (figure 2) using a Visual BASIC (Hamdy,
- program to obtain the corresponding derivative curves (Wahbi, 1991). The second order, D 2 curve was found to possess optima at the mean wavelengths 265, 273 and 281 nm. The fourth order, D 4 curve was found to possess optima at the mean wavelengths 267, 271, 277 and 279 nm.
Table 1 shows the results obtained for the determination of ibuprofen in tablets using second and fourth order derivative curves at the selected optima. The results were found to be within ±5% of the labeled amount (table 1).
Specificity The D 2 and D 4 curves for tablet solutions and reference solutions of ibuprofen in the solvent used were found to be coinciding with each other (within ± 1nm) with regard to position of optima (figure 2).
Linearity D 2 at 265 nm and D 4 271 nm for ibuprofen were found to be linearly related to concentration over the concentration range 80 to 280 μg/ml. Regression analysis of the linear relationship is shown in table 2.
Application of a curve fitting method and principle An absorption curve f (λ) can be represented as a polynomial equation of the form:
f (λ) = A + B λ + C λ^2 + D λ^3 + E λ^4 +……… (4)
where A, B, C, D, E etc are the coefficients of the constant, linear, quadratic, cubic, quartic etc components of the absorption curve, respectively. The curve fitting process is carried out to minimize the error, e, in the difference
f (λ) –[ A + B λ + C λ^2 + D λ^3 + E λ^4 +……] = e (5)
Calculating the coefficient, C, of the quadratic term C λ^2 will be highly representing an absorption curve quadratic in nature, and will not be affected by the constant or linear irrelevant absorption. BASIC programs are available that
Abdel Aziz Wahbi et al. 5
facilitate the calculation of C, or any other required coefficient from a set of absorbance measurements at a defined set of wavelengths (Wahbi, 1993). The coefficient, C, is linearly related to concentration, highly reproducible, specific to the analyzed compound and independent of constant and linear components of the substance absorption curve and irrelevant absorption curve. Using a standard ibuprofen solution with concentration C (^) s, the concentration of the tablet solution Ct can be obtained.
Choice of wavelengths Certain wavelengths in the absorption curve of ibuprofen have been selected. These points were chosen to coincide with the maxima, minima and shoulders of the absorption characteristics of ibuprofen. These were: 243, 249, 254, 258, 261, 264, 269, 272 and 273nm. A curve fitting BASIC program has been applied to calculate the quadratic coefficient, C.
Ibuprofen in tablets has been determined using the above mentioned curve fitting process at the selected wavelengths. The results obtained are shown in table 1. The results obtained were found to be within ±5% of the labeled amount.
Specificity The absorption curve of the tablet solution was found to possess two maxima at 264 and 272nm and a shoulder at 258 nm. This coincides with the absorption characteristics of ibuprofen. Furthermore, the compensation technique proved that interferences were found to be a non- specific constant curve.
Linearity The coefficient of the quadratic term, C for ibuprofen was found to be linearly related to concentration over the concentration range 80 to 280 μg/ml. The regression analysis of the linear relationship is shown in table 2.
Application of the B.P. 2003 HPLC reference method for the determination of ibuprofen in tablets The HPLC method of the B.P. 2003 has been applied to assay ibuprofen in tablets. Solutions of ibuprofen standard and tablets of concentration 0.2% w/v were prepared and analyzed.
Retention times of ibuprofen for sample and reference solutions were found to be 4.50 and 4.51 min, respectively. This confirms identification and specificity of ibuprofen. Table 1 shows the results obtained for the analysis of
Table 2 Collective table for the determination of ibuprofen in tablets using different methods and paired comparison
% Found per tablet
Method
Product Compensation (^) ∆A D 2 D 4 C HPLC
A 100.7 100.8 101.7 101.1 100.4 103.
B 99.7 99.0 99.7 99.4 99.5 98.
C 99.2 98.2 98.5 98.5 98.9 98.
D 97.2 98.6 97.7 98.4 97.6 99.
E 103.0 102.2 102.2 102.1 102.2 101.
Mean of differences *^ -0.1 -0.3 -0.1 -0.16 -0.
S.D. of difference 2.08 1.39 1.45 1.40 1.
S.E. = S.D.√ 5 0.93 0.62 0.65 0.62 0.
Confidence ++^ limits (^) ± 2.4 ± 1.6 ± 1.7 ± 1.6 ± 2.
***** Difference between % found of each method and the HPLC method for each product.
