- British Pharmacopoeia Volume III
- Formulated Preparations: Specific Monographs
Ibuprofen Gel |
Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.
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.
95.0 to 105.0% of the stated amount.
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Shake vigorously a quantity of the gel containing 0.125 g of Ibuprofen with 25 mL of dichloromethane for 5 minutes and use the upper layer.
(2) 0.5% w/v of ibuprofen BPCRS in dichloromethane.
(a) Use as the coating silica gel H.
(b) Use the mobile phase as described below.
(c) Apply 5 µL of each solution.
(d) Develop the plate to 10 cm.
(e) After removal of the plate, dry it at 120° for 30 minutes, lightly spray the plate with a 1% w/v solution of potassium permanganate in 1m sulfuric acid, heat at 120° for 20 minutes and examine under ultraviolet light (365 nm).
5 volumes of anhydrous acetic acid, 25 volumes of ethyl acetate and 75 volumes of n-hexane.
The principal spot in the chromatogram obtained with solution (1) corresponds in position and colour to that in the chromatogram obtained with solution (2).
B. In the Assay the retention time of the principal peak in the chromatogram obtained with solution (1) is the same as that of the principal peak in the chromatogram obtained with solution (2).
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Disperse a quantity of the gel containing 0.1 g of Ibuprofen in 25 mL of warm methanol, cool and dilute to 50 mL with methanol.
(2) Dilute 1 volume of solution (1) to 100 volumes with methanol.
(3) Dissolve 50 mg of ibuprofen BPCRS in 2.5 mL of a 0.006% w/v solution of ibuprofen impurity B BPCRS in methanol (prepared by diluting 1 volume of ibuprofen impurity B BPCRS to 10 volumes with methanol) and add sufficient methanol to produce 25 mL.
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Spherisorb ODS 2 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 214 nm.
(f) Inject 20 µL of each solution.
(g) Equilibrate the column with the mobile phase for about 45 minutes before starting the chromatography.
(h) Allow the chromatography to proceed for 1.5 times the retention time of the principal peak. When the chromatograms are recorded under the conditions described above, the retention time of ibuprofen is about 20 minutes.
0.5 volume of orthophosphoric acid, 340 volumes of acetonitrile and 600 volumes of water diluted to 1000 volumes with water. Equilibrate the column with the mobile phase for about 45 minutes before starting the chromatography.
In the chromatogram obtained with solution (3) measure the height (a) of the peak due to 2-(4-butylphenyl)-propionic acid and the height (b) of the lowest point of the curve separating this peak from that due to ibuprofen. The test is not valid unless a is greater than 1.5b. If necessary, adjust the concentration of acetonitrile in the mobile phase to obtain the required resolution.
In the chromatogram obtained with solution (1):
the area of any peak corresponding to ibuprofen impurity B is not greater than the area of the corresponding peak in the chromatogram obtained with solution (3) (0.3%);
the area of any other secondary peak is not greater than 0.3 times the area of the principal peak in the chromatogram obtained with solution (2) (0.3%);
the sum of the area of any secondary peaks, other than the peak due to impurity B, is not greater than 0.7 times the area of the principal peak in the chromatogram obtained with solution (2) (0.7%).
Disregard any peak the area of which is less than 0.1 times the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Disperse a quantity of the gel containing 50 mg of Ibuprofen with 50 mL of warm methanol for 10 minutes, cool and add sufficient methanol to produce 100 mL. Dilute 10 volumes of this solution to 20 volumes with the mobile phase.
(2) Dilute 10 volumes of a solution containing 0.05% w/v of ibuprofen BPCRS in methanol to 20 volumes with the mobile phase.
(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.
3 volumes of orthophosphoric acid, 247 volumes of water and 750 volumes of methanol.
Calculate the content of C13H18O2 using the declared content of C13H18O2 in ibuprofen BPCRS.
The impurities limited by the requirements of this monograph include:
1. (2RS)-2-(4-butylphenyl)propanoic acid (Ibuprofen Impurity B).