Miconazole and Hydrocortisone Acetate Cream

General Notices

Action and use

Antifungal azole.

Definition

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.

Content of miconazole nitrate, C18H14Cl4N2O,HNO3

95.0 to 105.0% of the stated amount.

Content of hydrocortisone acetate, C23H32O6

95.0 to 105.0% of the stated amount.

Identification

A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(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.
(2) 0.3% w/v of miconazole nitrate BPCRS in methanol.
(3) 0.15% w/v of hydrocortisone acetate BPCRS in methanol.
(4) 0.15% w/v of hydrocortisone BPCRS and 0.15% w/v of hydrocortisone acetate BPCRS in methanol.
chromatographic conditions
(a) Use as the coating silica gel F254 (Merck silica gel 60 F254 plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 10 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in air, expose to iodine vapour until spots appear and examine in daylight.
mobile phase

20 volumes of ammonium acetate solution, 40 volumes of dioxan and 40 volumes of methanol.

system suitability

The test is not valid unless the chromatogram obtained with solution (4) shows two clearly separated spots.

confirmation

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 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).

Tests

Acidity

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

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(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).
(2) Dilute 1 volume of solution (1) to 200 volumes with methanol.
(3) 0.02% w/v each of miconazole impurity A BPCRS and 2,4-dichlorobenzenemethanol in methanol.
chromatographic conditions
(a) Use 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) Use gradient 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 235 nm.
(f) Inject 20 µL of each solution.

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

mobile phase
Mobile phase A0.01m ammonium dihydrogen orthophosphate adjusted to pH 6.0 with dilute ammonia R1.
Mobile phase B10 volumes of tetrahydrofuran and 90 volumes of acetonitrile.
system suitability

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.

limits

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%);

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%).

Assay

For miconazole nitrate

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(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.
(2) 0.050% w/v of miconazole nitrate BPCRS in methanol.
(3) 0.02% w/v each of miconazole impurity A BPCRS and 2,4-dichlorobenzenemethanol.
chromatographic conditions

The chromatographic conditions described under Related substances may be used.

system suitability

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.

determination of content

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

For hydrocortisone acetate

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(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.
(2) 0.025% w/v of hydrocortisone acetate BPCRS in methanol.
(3) 0.02% w/v each of miconazole impurity A BPCRS and 2,4 –dichlorobenzenemethanol in methanol.

The chromatographic conditions described under Related substances may be used.

system suitability

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.

determination of content

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

IMPURITIES

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.