Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Antifungal.
DEFINITION
Econazole Cream contains Econazole Nitrate in a suitable basis.
The cream complies with the requirements stated under Topical Semi-solid Preparations and with the following requirements.
Content of econazole nitrate, C18H15Cl3N2O,HNO3
90.0 to 110.0% of the stated amount.
IDENTIFICATION
A. Mix a quantity of the cream containing 40 mg of Econazole Nitrate with 20 mL of a mixture of 1 volume of 1M sulfuric acid and 4 volumes of methanol and shake with two 50-mL quantities of carbon tetrachloride discarding the organic layers. Make the aqueous phase alkaline with 2M ammonia and extract with two 40-mL quantities of chloroform. Combine the chloroform extracts, shake with 5 g of anhydrous sodium sulfate, filter and dilute the filtrate to 100 mL with chloroform. Evaporate 50 mL to dryness and dissolve the residue in 50 mL of a mixture of 1 volume of 0.1M hydrochloric acid and 9 volumes of propan-2-ol. The light absorption of the resulting solution, Appendix II B, in the range 240 to 350 nm exhibits maxima at 265, 271 and 280 nm. The ratio of the absorbance at the maximum at 271 nm to that at the maximum at 280 nm is 1.55 to 1.77. The test is not valid unless the ratio of the absorbance in the test for resolution is at least 2.
B. In the Assay, the principal peak in the chromatogram obtained with solution (3) has the same retention time as the peak due to econazole in the chromatogram obtained with solution (4).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
Buffer Solution
Dissolve 2.5 g of potassium dihydrogen orthophosphate and 2.5 g of dipotassium hydrogen orthophosphate in 1000 mL of water.
(1) 0.05% w/v solution of miconazole nitrate in methanol (internal standard solution).
(2) Mix a quantity of the cream containing 10 mg of Econazole Nitrate with 20 mL of internal standard solution and 55 mL of methanol, warm on a water-bath for 30 seconds, shake for 1 minute, repeat the process twice and add 25 mL of buffer solution. Cool in an ice bath for 15 minutes, centrifuge for 10 minutes and use the supernatant liquid, filtered if necessary.
(3) Prepare in the same manner as solution (2) but using 20 mL of methanol in place of internal standard solution.
(4) 10 mL of a 0.1% w/v solution of econazole nitrate BPCRS in methanol with 20 mL of internal standard solution, 45 mL of methanol and 25 mL of buffer solution.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (20 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Hypersil ODS is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2.0 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 232 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
1 volume of buffer solution and 3 volumes of methanol.
DETERMINATION OF CONTENT
Calculate the content of C18H15Cl3N2O,HNO3 in the cream using the declared content of C18H15Cl3N2O,HNO3 in econazole nitrate BPCRS.
STORAGE
If Econazole Cream is kept in aluminium tubes, their inner surfaces should be coated with a suitable lacquer.
