Isoconazole Pessaries

Isoconazole Vaginal Tablets

Antifungal.

Isoconazole Pessaries are vaginal tablets containing Isoconazole Nitrate in a suitable basis.

The pessaries comply with the requirements stated under Vaginal 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 a quantity of powdered pessaries containing 10 mg of Isoconazole Nitrate with 10 mL of dichloromethane for 5 minutes and filter.

(2) 0.10% w/v of isoconazole nitrate BPCRS in dichloromethane.

(a) Use a silica gel precoated plate (Merck silica gel 60 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 and spray with potassium iodobismuthate solution.

10 volumes of methanol, 30 volumes of dichloromethane and 60 volumes of hexane.

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, the chromatogram obtained with solution (1) shows a peak with the same retention time as 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 a quantity of powdered pessaries containing 0.10 g of Isoconazole Nitrate with 10 mL of the mobile phase for 30 minutes and filter.

(2) Dilute 1 volume of solution (1) to 400 volumes with the mobile phase.

(3) 0.0025% w/v each of isoconazole nitrate BPCRS and of econazole nitrate BPCRS in the mobile phase.

(a) Use a stainless steel column (10 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (3 µm) (Hypersil ODS 3 µm 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 235 nm.

(f) Inject 20 µL of each solution.

(g) In the chromatogram obtained with solution (3) the approximate retention times of econazole and isoconazole are 10 minutes and 14 minutes respectively.

6.0 g of ammonium acetate in a mixture of 300 mL of acetonitrile, 320 mL of methanol and 380 mL of water.

The test is not valid unless the resolution factor between the peaks due to econazole and isoconazole in solution (3) is at least 5.0. 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%);

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%).

Disregard any peaks due to the solvent and to the nitrate ion and any peak with an area less than 0.4 times that 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 a quantity of the powdered pessaries containing 0.10 g of Isoconazole Nitrate with 100 mL of the mobile phase, mix and filter.

(2) 0.10% w/v of isoconazole nitrate BPCRS in the mobile phase.

(3) 0.10% w/v each of isoconazole nitrate BPCRS and of econazole nitrate BPCRS in the mobile phase.

The chromatographic conditions described under Related substances may be used.

The assay is not valid unless the resolution factor between the peaks due to econazole and isoconazole in solution (3) is at least 5.0. If necessary adjust the composition of the mobile phase.

Calculate the content of C₁₈H₁₄Cl₄N₂O,HNO₃ in the pessaries using the declared content of C₁₈H₁₄Cl₄N₂O,HNO₃ in isoconazole nitrate BPCRS.

The impurities limited by the requirements of this monograph include those listed in the monograph for Isoconazole Nitrate.