(Ph. Eur. 11.6 update)
Action and use
Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.
DEFINITION
Ibuprofen Oral Suspension is a suspension of Ibuprofen in a suitable flavoured vehicle.
The oral suspension complies with the requirements stated under Oral Liquids and with the following requirements.
Content of ibuprofen, C13H18O2
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of the oral suspension containing 0.5 g of Ibuprofen with 25 mL of dichloromethane and 15 mL of water. Allow to stand until the layers have separated and discard the upper layer. Shake the lower layer with 5 mL of water and discard the upper layer. Evaporate the lower layer to dryness, add 20 mL of water to the residue and filter (Whatman GF/C filter is suitable). Wash the residue with 20 mL of dichloromethane and evaporate to dryness. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of ibuprofen (RS 186).
TESTS
Dissolution
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 2, rotating the paddle at 50 revolutions per minute.
(b) Use 900 mL of phosphate buffer pH 7.2, at a temperature of 37°, as the medium.
PROCEDURE
Carry out the method for liquid chromatography, Appendix II D, using the following solutions.
(1) Shake the oral suspension for 30 seconds and place a volume of the oral suspension containing 0.2 g of Ibuprofen into each dissolution vessel. After 30 minutes, withdraw a sample of the medium, filter and dilute, if necessary, with the dissolution medium to produce a solution expected to contain 0.022% w/v of Ibuprofen.
(2) 0.022% w/v of ibuprofen BPCRS in the dissolution medium.
(3) 0.15% w/v each of benzophenone and ibuprofen BPCRS in acetonitrile. Dilute 1 volume to 10 volumes with the dissolution medium.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octylsilyl silica gel for chromatography (5 μm).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 220 nm.
(f) Inject 10 μL of each solution.
MOBILE PHASE
37 volumes of acetonitrile and 63 volumes of 0.01M orthophosphoric acid.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to benzophenone and ibuprofen is at least 1.5.
DETERMINATION OF CONTENT
Calculate the total content of ibuprofen, C13H18O2, in the medium using the declared content of C13H18O2 in ibuprofen BPCRS.
LIMITS
The amount of ibuprofen released is not less than 75% (Q) of the stated amount.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions immediately after preparation.
(1) Disperse with the aid of ultrasound a quantity of the oral suspension containing 0.2 g of Ibuprofen with 20 mL of acetonitrile R1. Add sufficient mobile phase A to produce 100 mL and filter (Whatman GF/C is suitable).
(2) Dilute 1 volume of solution (1) to 100 volumes with mobile phase A. Further dilute 1 volume to 10 volumes with mobile phase A.
(3) Dissolve 20 mg of ibuprofen BPCRS in 2 mL of acetonitrile R1 , add 1 mL of a 0.006% w/v solution of ibuprofen impurity B BPCRS in acetonitrile R1, and dilute to 10 mL with mobile phase A.
(4) 0.0006% w/v of 4′-isobutylacetophenone BPCRS (impurity E) in mobile phase A.
(5) Dissolve the contents of a vial of ibuprofen for peak identification EPCRS in 1 mL of acetonitrile R1, and dilute to 5 mL with mobile phase A.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with end-capped octadecylsilyl amorphous organosilica polymer for chromatography (5 μm) (XTerra MS C18 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 214 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
Mobile phase A 0.5 volume of orthophosphoric acid, 340 volumes of acetonitrile R1 and sufficient water to produce 1000 volumes.
Mobile phase B 0.5 volume of orthophosphoric acid, 100 volumes of water and sufficient acetonitrile R1 to produce 1000 volumes.
| Time (Minutes) | Mobile phase A (% v/v) | Mobile phase B (% v/v) | Comment |
| 0-25 | 100 | 0 | isocratic |
| 25-55 | 100→0 | 0→100 | linear gradient |
| 55-70 | 0 | 100 | isocratic |
| 70-71 | 0→100 | 100→0 | linear gradient |
| 71-85 | 100 | 0 | re-equilibration |
When chromatograms are recorded under the prescribed conditions, the relative retentions with reference to ibuprofen (retention time about 26 minutes) are: impurity J, about 0.2; impurity N, about 0.3; impurity A, about 0.9; impurity B, about 1.08 and impurity E, about 1.11.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the peak-to-valley ratio is at least 5.0, where Hp is the height above the baseline of the peak due to impurity B and Hv is the height above the baseline of the lowest point of the curve separating this peak from the peak due to ibuprofen.
LIMITS
Use the chromatogram supplied with ibuprofen for peak identification EPCRS and the chromatogram obtained with solution (5) to identify the peaks due to impurities A, J, and N. Use the chromatogram obtained with solution (4) to identify the peaks due to impurity E.
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity E is not greater than 3 times the area of the principal peak in the chromatogram obtained with solution (2) (0.3%);
the area of any peak corresponding to impurity A, J or N is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.15% of each);
the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.1%);
the sum of the areas of any secondary peaks is not greater than 7 times the area of the principal peak in the chromatogram obtained with solution (2) (0.7%).
Disregard any peak with an area less than half the area of the principal peak in the chromatogram obtained with solution (2) (0.05%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions immediately after preparation.
(1) Mix a weighed quantity of the mixed oral suspension containing 0.1 g of Ibuprofen with 30 mL of acetonitrile, add a further 10 mL of acetonitrile and 10 mL of 0.01M orthophosphoric acid, shake vigorously, dilute to 100 mL with 0.01M orthophosphoric acid and filter (Whatman GF/C paper is suitable).
(2) 0.1% w/v of ibuprofen BPCRS prepared by dissolving a suitable quantity in 40 volumes of acetonitrile and adding 60 volumes of 0.01M orthophosphoric acid.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (30 cm × 3.9 mm) packed with end-capped octadecylsilyl silica gel for chromatography (10 μm) (μBondapak C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 220 nm.
(f) Inject 10 μL of each solution.
MOBILE PHASE
4 volumes of acetonitrile and 6 volumes of 0.01M orthophosphoric acid.
When the chromatograms are recorded under the prescribed conditions the retention time of ibuprofen is about 21 minutes.
DETERMINATION OF CONTENT
Determine the weight per mL of the oral suspension, Appendix V G, and calculate the content of C13H18O2, weight in volume, from the declared content of C13H18O2 in ibuprofen BPCRS.
STORAGE
Ibuprofen Oral Suspension should be protected from light.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Ibuprofen.
