Miconazole Cream

Antifungal azole.

Miconazole Cream contains Miconazole Nitrate 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. Mix a quantity containing 40 mg of Miconazole 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 hexane, 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 methanol. The light absorption of the resulting solution, Appendix II B, in the range 230 to 350 nm exhibits maxima at 264, 272 and 280 nm.

B. In the Assay, the principal peak in the chromatogram obtained with solution (1) has the same retention time as the peak due to miconazole in the chromatogram obtained with solution (2).

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of the cream containing 50 mg of Miconazole Nitrate with 30 mL of a mixture of equal volumes of methanol and tetrahydrofuran for 30 minutes, add sufficient of the same solvent mixture to produce 50 mL and filter through a glass microfibre filter (Whatman GF/C is suitable). For solution (2) dilute 5 volumes of solution (1) to 100 volumes with a mixture of equal volumes of methanol and tetrahydrofuran and 5 volumes of the resulting solution to 100 volumes with the same solvent mixture. Solution (3) contains 0.0025% w/v of miconazole nitrate BPCRS and 0.0025% w/v of econazole nitrate BPCRS in a mixture of equal volumes of methanol and tetrahydrofuran.

The chromatographic procedure may be carried out using (a) a stainless steel column (10 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (3 µm) (Hypersil 3 ODS is suitable), (b) as the mobile phase with a flow rate of 2 mL per minute a 0.6% w/v solution of ammonium acetate in a mixture of 300 volumes of acetonitrile, 320 volumes of methanol and 380 volumes of water and (c) a detection wavelength of 235 nm.

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks due to miconazole and econazole is at least 10. If necessary adjust the composition of the mobile phase.

In the chromatogram obtained with solution (1) the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.25%) and the sum of the areas of any secondary peaks is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of the cream containing 50 mg of Miconazole Nitrate with 30 mL of a mixture of equal volumes of methanol and tetrahydrofuran for 30 minutes, add sufficient of the same solvent mixture to produce 50 mL and filter through a glass microfibre filter (Whatman GF/C is suitable). Solution (2) contains 0.1% w/v of miconazole nitrate BPCRS in a mixture of equal volumes of methanol and tetrahydrofuran. Solution (3) contains 0.0025% w/v of miconazole nitrate BPCRS and 0.0025% w/v of econazole nitrate BPCRS in a mixture of equal volumes of methanol and tetrahydrofuran.

The chromatographic procedure described under Related substances may be used.

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks due to miconazole and econazole is at least 10. If necessary adjust the composition of the mobile phase.

Calculate the content of C₁₈H₁₄Cl₄N₂O,HNO₃ in the cream using the declared content of C₁₈H₁₄Cl₄N₂O,HNO₃ in miconazole nitrate BPCRS.

If Miconazole Cream is kept in aluminium tubes, their inner surfaces should be coated with a suitable lacquer.