Miconazole and Hydrocortisone Acetate Cream

Antifungal azole.

Miconazole and Hydrocortisone Acetate Cream contains Miconazole Nitrate and Hydrocortisone Acetate 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.

95.0 to 105.0% of the stated amount.

A.  Carry out the method for thin-layer chromatography, Appendix III  A, using a precoated silica gel F₂₅₄ plate (Merck silica gel 60 F₂₅₄ plates are suitable) and a mixture of 20  volumes of ammonium acetate, 40  volumes of dioxan and 40  volumes of methanol as the mobile phase. Apply separately to the plate 10  µl of each of the following solutions. For solution (1) disperse a quantity of the cream containing 0.15  g of Miconazole Nitrate by shaking with 25  ml of methanol for about 30 minutes, dilute to 50  ml with methanol, filter and use the filtrate. Solution (2) contains 0.3% w/v of miconazole nitrate BPCRS in methanol. Solution (3) contains 0.15%  w/v of hydrocortisone acetate BPCRS in methanol. Solution (4) contains 0.15%  w/v of hydrocortisone BPCRS and 0.15%  w/v of hydrocortisone acetate BPCRS in methanol. After removal of the plate, allow it to dry in air, expose to iodine vapour until spots appear and examine in daylight. The principal spots in the chromatogram obtained with solution (1) are similar in position, colour and size to those in the chromatograms obtained with solutions (2) and (3). The test is not valid unless the chromatogram obtained with solution (4) shows two clearly separated spots.

B.  In the Assay for miconazole nitrate, the chromatogram obtained with solution (1) shows a peak with the same retention time as the peak due to miconazole nitrate in the chromatogram obtained with solution (2).

C.  In the Assay for hydrocortisone acetate, the chromatogram obtained with solution (1) shows a peak with the same retention time as the peak due to hydrocortisone acetate in the chromatogram obtained with solution (2).

pH of a 10% w/v dispersion in carbon dioxide-free water, 3.5 to 4.5, Appendix V L.

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of the cream containing 25 mg of Miconazole Nitrate with 30 ml of methanol for 30 minutes, add sufficient methanol to produce 50 ml and filter (Whatman GF/F is suitable). For solution (2) dilute 1 volume of solution (1) to 200 volumes with methanol. Solution (3) contains 0.02% w/v each of miconazole impurity A EPCRS and 2,4-dichlorobenzenemethanol in methanol.

The chromatographic procedure may be carried out using (a) a stainless steel column (10 cm × 4.6 mm) packed with base-deactivated, end-capped octadecylsilyl silica gel for chromatography (3 µm) (Hypersil BDS is suitable), (b) as the mobile phase with a flow rate of 1.5 ml per minute the changing proportions of mobile phases A and B described below and (c) a detection wavelength of 235 nm.

Inject 20 µl of each solution.

Mobile phase A  A solution containing 0.01m ammonium dihydrogen orthophosphate adjusted to pH 6.0 with dilute ammonia R1.

Mobile phase B  A mixture of 10 volumes of tetrahydrofuran and 90 volumes of acetonitrile.

When the chromatograms are recorded under the prescribed conditions the retention times are: hydrocortisone acetate, about 8 minutes; miconazole, about 18 minutes.

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is greater than 5.0.

In the chromatogram obtained with solution (1), the area of any peak other than those of Hydrocortisone acetate and Miconazole is not greater than the area of the miconazole peak in the chromatogram obtained with solution (2) (0.5%) and the sum of the areas of any such peaks is not greater than five times the area of the principal peak in the chromatogram obtained with solution (2) (2.5%). Disregard any peak due to nitrate ion and any peak with an area less than 0.2 times the area of the peak in the chromatogram obtained with solution (2) (0.1%).

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 50 ml of methanol for 15 minutes, add sufficient methanol to produce 100 ml and filter if necessary. Solution (2) contains 0.050% w/v of miconazole nitrate BPCRS in methanol. Solution (3) contains 0.02% w/v each of miconazole impurity A EPCRS and 2,4-dichlorobenzenemethanol.

The chromatographic conditions 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 two principal peaks is greater than 5.0.

Calculate the content of C₁₈H₁₄Cl₄N₂O in the preparation being examined using the declared content of C₁₈H₁₄Cl₄N₂O.HNO₃ in miconazole nitrate BPCRS.

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of the cream containing 25 mg of Hydrocortisone Acetate with 50 ml of methanol for 15 minutes, add sufficient methanol to produce 100 ml and filter if necessary. Solution (2) contains 0.025% w/v of hydrocortisone acetate BPCRS in methanol. Solution (3) contains 0.02% w/v each of miconazole impurity A EPCRS and 2,4-dichlorobenzenemethanol.

The chromatographic conditions 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 two principal peaks is greater than 5.0.

Calculate the content of C₂₃H₃₂O₆ in the preparation being examined using the declared content of C₂₃H₃₂O₆ in hydrocortisone acetate BPCRS.

The impurities limited by the requirements of this monograph include impurity A listed under Miconazole Nitrate and the following:

2,4-dichlorobenzenemethanol,

2,4-dichloro-β-[2,4-dichlorophenyl)-methoxy]benzene ethanamine,

N-[2-(2,4-dichlorophenyl)-2-[(2,4-dichlorophenyl)-methoxy]ethyl]formamide.