(Ph. Eur. 11.6 update)
Action and use
Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.
DEFINITION
Ibuprofen Gel is a solution of Ibuprofen in a suitable water-miscible basis.
The gel complies with the requirements stated under Topical Semi-solid Preparations and with the following requirements.
Content of ibuprofen, C13H18O2
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Disperse a quantity of the gel containing 0.5 g of Ibuprofen with 20 mL of methanol and prepare a solid phase extraction cartridge containing a silica sorbent (Discovery DSC-18 SPE cartridges are suitable) by passing through 2 mL of methanol and 3 mL of water. Mix 1 mL of the sample solution with 1.5 mL of acetic acid (2%) to produce a solution of pH 3.0. Pass the resulting solution through the cartridge, wash the cartridge with 1 mL of a 2% w/v solution of acetic acid and discard the eluent. Pass three 1 mL aliquots of methanol, collect the eluent 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
Acidity or alkalinity
The pH of the gel is 5.5 to 7.5, Appendix V L.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Disperse with the aid of ultrasound a quantity of the gel containing 0.2 g of Ibuprofen in 50 mL of mobile phase A, dilute to 100 mL with mobile phase A and filter (Whatman GF/C filter 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 peak 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 0.5 times 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.
(1) Disperse with the aid of ultrasound a weighed quantity of the gel containing 50 mg of Ibuprofen in 50 mL of methanol, dilute to 100 mL with methanol and filter (Whatman GF/C filter is suitable). Dilute 1 volume to 2 volumes with the mobile phase.
(2) 0.05% w/v of ibuprofen BPCRS in methanol. Dilute 1 volume to 2 volumes with the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (10 μm) (Nucleosil C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 264 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
3 volumes of orthophosphoric acid, 247 volumes of water and 750 volumes of methanol.
When the chromatograms are recorded under the prescribed conditions, the retention time of ibuprofen is about 7 minutes.
DETERMINATION OF CONTENT
Calculate the content of C13H18O2 in the gel using the declared content of C13H18O2 in ibuprofen BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Ibuprofen.
