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Category Antifungal (topical).

      Miconazole Nitrate Cream contains not less than 90.0 per cent and not more than 110.0 per cent of the labelled amount of C₁₈H₁₄C_l4N₂O.HNO₃.

Strength available 2 per cent w/w.

Dose Topical, to the skin, once or twice a day.

Contra-indication See under Clotrimazole, p. 83.

Warning; Precaution See under Miconazole Nitrate, p. 127.

Packaging and storage Miconazole Nitrate Cream shall be kept in tightly closed containers.

Identification

      A. Mix a quantity containing 40 mg of miconazole nitrate with 20 ml of a mixture of 1 volume of 1 M sulfuric acid and 4 volumes of methanol and shake with two 50-ml quantities of hexane UV, discarding the organic layers. Make the aqueous phase alkaline with 2 M 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 0.1 M hydrochloric acid and 9 volumes of methanol. The ultraviolet absorption spectrum of the resulting solution, when observed between 230 and 350 nm, exhibits three maxima at 264 nm, 272 nm and 280 nm (Appendix 2.2).

      B. The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.

Related substance Carry out the determination as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).

      Mobile phase, Resolution solution and Chromatographic system Proceed as directed in the Assay.

      Test solution (a) Use the Assay preparation.

      Test solution (b) Dilute 5 volumes of Test solution (a) to 100 volumes with a mixture of equal volumes of methanol and tetrahydrofuran and dilute 5 volumes of the resulting solution to 100 volumes with the same solvent mixture.

      Procedure Separately inject equal volumes (about 10 μl) of Test solution (a) and Test solution (b) into the chromatograph, record the chromatograms and measure the responses for the major peaks. In the chromatogram obtained from Test solution (a), the area of any secondary peak is not more than area of the principal peak in the chromatogram obtained from Test solution (b) (0.25 per cent); the sum of the areas of any secondary peaks is not more than twice the area of the principal peak in the chromatogram obtained from Test solution (b) (0.5 per cent).

Assay Carry out the determination as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).

      Mobile phase Prepare a solution of 6.0 g of ammonium acetate in a mixture of 300 ml of acetonitrile, 320 ml of methanol and 380 ml of water. Make adjustments if necessary.

      Standard preparation Dissolve about 50 mg of Miconazole Nitrate RS, accurately weighted, in a sufficient amount of a mixture of equal volumes of methanol and tetrahydrofuran and dilute to 50.0 ml with the same solvent. Resolution solution Dissolve 2.5 mg of Miconazole Nitrate RS and 2.5 mg of Econazole Nitrate RS in a mixture of equal volumes of methanol and tetrahydrofuran and dilute to 100.0 ml with the same solvent. Assay preparation Shake an accurately measured quantity of Miconazole Nitrate Cream containing about 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 50.0 ml and filter.

      Resolution solution Dissolve 2.5 mg of Miconazole Nitrate RS and 2.5 mg of Econazole Nitrate RS in a mixture of equal volumes of methanol and tetrahydrofuran and dilute to 100.0 ml with the same solvent.

      Assay preparation Shake an accurately measured quantity of Miconazole Nitrate Cream containing about 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 50.0 ml and filter.

      Chromatographic system The chromatographic procedure may be carried out using (a) a stainless steel column (10 cm × 4.6 mm) packed with octadecylsilane chemically bonded to porous silica particles (3 μm), (b) Mobile phase at a flow rate of about 2 ml per minute and (c) an ultraviolet photometer set at 235 nm.

      To determine the suitability of the chromatographic system, chromatograph Resolution solution, and record the peak responses as directed under Procedure: the resolution factor between the miconazole and econazole peaks is not less than 10. Chromatograph Standard preparation, and record the peak responses as directed under Procedure: the relative standard deviation for replicate injections is not more than 2.0 per cent.

      Procedure Separately inject equal volumes (about 10 μl) of Standard preparation and Assay preparation into the chromatograph, record the chromatograms and measure the responses for the major peaks. 

      Calculation Calculate the content of C₁₈H₁₄C_l4N₂O.HNO₃ in the portion of the Cream taken, using the declared content of C₁₈H₁₄Cl₄N₂O.HNO₃ in Miconazole Nitrate RS.

Other requirements Comply with the requirements described under “Topical Semi-solid Preparations” (Appendix 1.16).