INTRODUCTION:

Ibuprofen is chemically 2[4-(2-methyl propyl) phenyl] propanoic acid. The structural formula is C₁₃H₁₈O₂, and molecular weight is 206. It is used for relief of symptoms of arthritis, primary dysmenorrheal, and fever and as an analgesic^1-3. Ibuprofen is the most commonly used and most frequently prescribed NSAID^4,5. It is a non-selective inhibitor of cyclo-oxygenase-1 (COX-1) and Cyclooxygenase-2 (COX-2)⁶ Although its anti inflammatory properties may be weaker than those of some other NSAIDs, it has a prominent analgesic and antipyretic role. Its effects are due to the inhibitory actions on cyclo-oxygenases, which are involved in the synthesis of prostaglandins. Prostaglandins have an important role in the production of pain, inflammation and fever⁷.Ibuprofen is known to have an anti platelet (blood-thinning effect)⁸. Ibuprofen was developed by the Boots Group in the 1960s⁹. It was discovered by Andrew RM Dunlop, with colleagues Stewart Adams, John Nicholson, Vonleigh Simmons, Jeff Wilson and Colin Burrows and was patented in 1961. The drug was launched as a treatment for rheumatoid arthritis in the United Kingdom in 1969, and in the United States in 1974. Dr. Adams initially tested his drug on a hangover.

He was subsequently awarded an OBE in 1987. Boots was awarded the Queen's Award for Technical Achievement for the development of the drug in 1987¹⁰. Various methods for analysis of the same are available but are time consuming and expensive. Ibuprofen Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of C₁₃H₁₈O₂. (Figure 1)

A through literature survey has revealed that a limited number of analytical methods have been reported for the determination of ibuprofen. From all these methods, spectrophotometric analysis serves to be the quickest, promising and reliable method for routine analytical needs.

The principal objective of this study was, therefore, to develop a new, sample, economical, selective, precise, reproducible, validated analytical and bioanalytical method development of ibuprofen in bulk and tablets by UV-spectroscopy. In this method proposed the sodium hydroxide used directly for dilution of the preparation after filtration and further used for analysis. Direct use of solvent sodium hydroxide as diluents for formulation in analysis to minimizes errors during procedure.

MATERIAL:

Ibuprofen pure drug was obtained as a gift sample from BPL Pharmaceuticals (P) Ltd. Mumbai. Brufen 400 tablets of ibuprofen were purchased from market. All the reagents used in this assay were of analytical grade and the reagent solutions were prepared using preanalysed double distilled water.

Figure 1: Structural Formula of Ibuprofen

Apparatus:

Spectral runs were made on a Shimadzu UV-Visible spectrophotometer, model- 1800 (Japan) was employed with spectral bandwidth of 1 nm and wavelength accuracy of ± 0.3 nm with automatic wavelength corrections with a pair of 10 mm quartz cells. Glass wares used in each procedure were soaked overnight in a mixture of chromic acid and sulphuric acid rinsed thoroughly with double distilled water and dried in hot air oven.

EXPERIMENTAL:

Standard Stock Solution:

Accurately weighed ibuprofen (10mg) was transferred to a 100ml volumetric flask, dissolved in 10ml with 0.1 N sodium hydroxide and made up the volume up to the mark with 0.1 N sodium hydroxide. A stock solution contained 100mcg/ml of ibuprofen.

Determination of λ max:

Weighed an accurate amount 10mg of ibuprofen was dissolved in 10ml 0.1 N sodium hydroxide and diluted up to 100ml by same to obtain a 100mcg/ml concentration of ibuprofen in solution. This solution was subjected to scanning between 200 – 400 nm. The effect of dilution on absorption maxima was studied by diluting the above solution to 25mcg/ml and scanned from 200 – 400nm.

Figure 2: Calibration Curve of Ibuprofen at 221 nm

Preparation of calibration curve for ibuprofen:

Stock solutions of ibuprofen (0.2ml to 2.0ml) were pipetted out in to a series of ten volumetric flask of 10ml. the volume in each volumetric flask was made up to the mark with 0.1 N sodium hydroxide. It produced the concentration range of 2-20 mcg/ml of ibuprofen. The absorbance of the solution was measured at 221nm against 0.1 N sodium hydroxide as a blank Table 1. The calibration curve was given in figure 2 and statistical parameters like the slope, intercept, coefficient of correlation, and optical characteristics are summarized in Table 2.

Table 1: Data for Calibration Curve of Ibuprofen

S. No.	Concentration (µg/ml)	Absorbance	Regressed Absorbance
1	2	0.145	0.1837
2	4	0.388	0.3093
3	6	0.407	0.4349
4	8	0.536	0.5605
5	10	0.652	0.6861
6	12	0.895	0.8117
7	14	0.9	0.9373
8	16	1.073	1.0629
9	18	1.186	1.1885
10	20	1.312	1.3141

Table No. 2: Optical Characteristics and Other Parameters

Absorption maxima	221 nm
Beer's law limit	2-20 mcg/ml
Coefficient of Correlation	1
Regression equation (y=a+bc)	y = 0.0581+0.06283x
Slope (b)	0.1256
y intercept (a)	0.0581

Analysis of Marketed Tablet Formulation:

Accurately weighed the 20 tablets of Brufen400 and fine powdered. The powder equivalent to 100mg of ibuprofen was transferred to 100ml volumetric flask and 20ml 0.1 N sodium hydroxide is added and sonicated for 15 minutes to dissolve the ibuprofen in it and made the volume to mark with same. The solution was filtered through Whatman filter paper No. 40. 10ml of this solution was diluted with 0.1 N sodium and determined the absorbance at 221nm against the 0.1 N sodium hydroxide diluted with same as blank. The concentration of ibuprofen present in marketed tablet formulation were determined, Table 3.

Table 3: Result of Analysis of Ibuprofen in Tablet (Brufen 400)

Formu lation	Label claim (mg)	Amount found	% Label Claim found ±SD
Brufen 400	400	399.21	99.80±0.12

n=3

Recovery studies:

Recovery studies were performed to judge the accuracy of the method. 1ml of standard formulation (100mcg/ml) was taken in three 10ml volumetric flask and to it 80%, 100% and 120% (i.e. 0.8ml, 1.0ml, 1.2ml) of working standard solution (100mcg/ml) added respectively and made the volume up to the mark. The respective absorbance at 221nm was recorded against the blank. The amount of added concentration was determined from the obtained absorbance values and percent recovery was determined for formulation Table 4.

Table 4: Recovery Study

S. NO.	% of solution	Amount recovered (µg/ml)	Actual amount added	% reco very	Mean recovery ±SD
1	80	7.886	7.986	98.78	99.20
2	100	9.921	9.952	99.69
3	120	11.851	11.956	99.12

n=3

EVALUATION OF TABLETS OF IBUPROFEN:

The ibuprofen tablets were evaluated for various parameters like weight variation, friability, hardness, disintegration, dissolution and result reported in table.

Weight variation test

The variation of the weight of individual tablets is a valid indication of the corresponding variation in the drug content¹¹. The average tablet weight was determined by weighing 20 tablets individually by using an analytical balance¹². The mean ± S.D. of formulation is mention in Table 5.

Table 5: Weight Variation Study

S. No.	Weight of tablet ±SD (mg)	Average Weight ±SD (mg)	Result
1	550±0.01	551.50±0.02	Pass
2	550±0.01		Pass
3	560±0.01		Pass
4	553±0.02		Pass
5	550±0.01		Pass
6	555±0.03		Pass
7	550±0.02		Pass
8	550±0.01		Pass
9	550±0.02		Pass
10	550±0.01		Pass
11	550±0.01		Pass
12	550±0.03		Pass
13	552±0.01		Pass
14	550±0.02		Pass
15	560±0.01		Pass
16	550±0.01		Pass
17	550±0.01		Pass
18	550±0.03		Pass
19	550±0.01		Pass
20	552±0.02		Pass

n=3

Crushing strength or hardness determination:

Hardness of the tablets was determined by using Monsanto and Pfizer Hardness Tester¹³. The mean ± S.D of tablets is shown in Table 6.

Table 6: Hardness

Tablet	Hardness (kg/cm²) ±SD
1	5.1±0.11
2	5.4±0.09
3	5.3±0.09
4	5.4±0.10
5	5.5±0.08
6	5.7±0.10

n=3

Friability testing:

Six tablets were taken and loose dust was removed with the aid of air pressure or a soft brush. Tablet samples were weighed accurately and friability determined in Roche Friabilator (USP XXIII, Electrolab, Mumbai, India). After the given number of rotations (100 rotations for 4 min at 25 rpm) loose dust was removed from the tablets as before. Finally tablets were weighed. The loss in weight indicates the ability of the tablets to withstand this type of wear (British Pharmacopoeia, 2004).The percent friability was determined by using following formula ¹¹:-

% friability = (initial weight- final weight) x 100

Initial weight

In vitro Disintegration test

Disintegration is evaluated to ensure that the drug substance is fully available for dissolution and absorption from the gastrointestinal tract¹¹. Disintegration time was measured for 6 tablets by inserting disks using 900ml phosphate buffer (7.4 P^H) at 37±2ºC in USP disintegration test apparatus (Electrolab, Mumbai, India) Table 7.

Table 7: Disintegration Time

Tablet	Disintegration (min.) ±SD
1	5.45±0.02
2	6.25±0.05
3	6.71±0.03
4	7.34±0.01
5	5.53±0.02
6	6.72±0.09

n=3

In vitro Dissolution test

Dissolution of Ibuprofen tablets was conducted according to the USP Paddle dissolution test apparatus (Electrolab, Mumbai, India) method. The dissolution test was performed using 900 ml of pH 7.2 phosphate buffer solutions, as a dissolution medium, at a paddle speed of 50 rpm and maintained at 37 ± 0.5°C. The aliquots were withdrawn at different intervals and filtered through Whatman filter paper. The sample volume was replaced with an equal volume of fresh dissolution medium. The drug release was measured by using UV- Spectrophotometer at 221nm Table 8 and cumulative drug release profile represent in figure 3.

Table 8: In vitro Drug Release Profile

S. No.	Time (min.)	Percent Cumulative Drug Release
1	5	10.56±0.56
2	10	18.53±0.98
3	15	23.88±1.02
4	20	31.88±1.54
5	25	52.73±1.65
6	30	65.32±1.34
7	35	76.12±2.10
8	40	87.41±1.11
9	45	91.22±2.01
10	50	97.16±1.63

n=3

Figure 3. In vitro Cumulative Drug Release Profile

RESULT AND DISCUSSION:

The UV scan of standard solution between 200 – 400 nm showed the absorption maxima at 221nm. No effect of dilution was observed on the maxima, which confirmed the maxima at 221nm. The statistical analysis of data obtained for the calibration curve of ibuprofen in pure solution indicated a high level of precision for the proposed method, as evidenced by low value of coefficient of variation. The coefficient of correlation was highly significant. The linearity range was observed between 2 – 20 mcg/ml. The plot clearly showed a straight line passing through origin (Y=0.0581+0.06283x). The estimated method was validated by recovery study, indicating accuracy and precision of the methods. The results of analysis were validated by recovery studies. The recovery of the drug was more than 99%. The method was found to be simple, accurate, precise, economical and robust. Excellent recovery studies further proves the accuracy of the method.

The ibuprofen (Brufen 400) purchased from market and characterized of different parameters as summarized in Table 9. All the tablets passed weight variation test as the percentage weight variation was within the pharmacopoeial limits. Hardness and friability of marketed tablet were within acceptable limits. Hardness of the tablets was 5.1 to 5.7 kg/cm². The friability was found to be less than 1.0% and hence the tablets with lower friability and good hardness may not break during handling on machines and shipping. The in-vitro Disintegration time is very important for estimation of drug absorption. The in-vitro disintegration time was found in the range of 5.23 to 7.34 min. The in vitro dissolution study was performed in phosphate buffer (pH 7.2) since this approach is recommended in the USP. The dissolution study of the marketed formulation of ibuprofen tablets (400 mg) showed complete drug release within 50 minutes. The percentage drug release of marketed tablet shows the better drug release between 95.1 to 97.2%.

Table 9: Summery of Evaluation Parameters of Ibuprofen Marketed Tablets

Formulation	Weight variation	Hardness (kg/cm²)	friability	Disintegration time (min.)
Brufen 400	Passed	5.4±0.08	0.22±0.05	6.33±0.02

CONCLUSIONS:

From the results and discussion the method described in this paper for the determination of ibuprofen from tablet formulation is simple, accurate, sensitive reproducible and economical. The proposed method utilizes inexpensive solvents. The proposed method could be applied for routine analysis in quality control laboratories. The evaluation method of ibuprofen tablets may be helpful for characterization of similar formulation.

ACKNOWLEDGEMENTS:

Authors are sincerely thankful to Mahatma Gandhi College Of Pharmaceutical sciences Jaipur for providing necessary facilities for work.

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Received on 19.12.2010 Modified on 03.01.2011

Research J. Pharm. and Tech. 4(4): April 2011; Page 620-623