- British Pharmacopoeia Volume III
- Formulated Preparations: Specific Monographs
Ibuprofen Cream |
Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.
Ibuprofen Cream contains Ibuprofen in a suitable basis.
The cream 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 cream containing 50 mg of Ibuprofen with 10 mL of dichloromethane for 5 minutes and filter (Whatman GF/C paper is suitable).
(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, colour and size 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) corresponds to 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) Shake vigorously a quantity of the cream containing 0.1 g of Ibuprofen with 25 mL of methanol for 10 minutes, decant the solution into a 50 mL graduated flask, rinse the original flask with two 10-mL quantities of methanol, dilute the combined solution and rinsings to 50 mL with methanol and filter (Whatman GF/C paper is suitable).
(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) Equilibrate the column with the mobile phase for about 45 minutes before starting the chromatography.
(g) Inject 20 µL of each solution.
(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 after equilibration.
In the chromatogram obtained with solution (3) measure the height (a) of the peak due to (2RS)-2-(4-butylphenyl)-propanoic 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) Shake vigorously a quantity of the cream containing 50 mg of Ibuprofen with 25 mL of the mobile phase for 10 minutes, decant the solution into a 50 mL graduated flask, rinse the original flask with two 10-mL quantities of the mobile phase, dilute the combined solution and rinsings to 50 mL with the mobile phase and filter (Whatman GF/C paper is suitable).
(2) 0.1% w/v of ibuprofen BPCRS in 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 in the cream 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).