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Category Antiprotozoal; antibacterial.

      Metronidazole Tablets contain not less than 90.0 per cent and not more than 110.0 per cent of the labelled amount of C₆H₉N₃O₃.

Strengths available 200, 250, 400, and 500 mg

Dose Adults----Amebiasis: 500 to 750 mg three times a day for 5 to 10 days.

      Trichomoniasis: 2 g as a single dose; 1 g twice a day for 1 day; or 250 mg three times a day for 7 days.

      Anaerobic infection: Initially 800 mg, followed by 400 mg every 8 hours for 7 days.

      Ulcer, duodenal, Helicobacter pylori -associated: 500 mg three times a day, in conjunction with other suitable drugs, for one to two weeks.

      Children----Amebiasis: 11.6 to 16.7 mg per kg of body weight three times a day for 5 to 10 days.

      Trichomoniasis: 5 mg per kg of body weight three times a day for 7 days.

      Anaerobic infection: 7.5 to 10 mg per kg of body weight every 8 hours.

Contra-indication; Warning; Precaution; Additional information See under Metronidazole, p. 125.

Packaging and storage Metronidazole Tablets shall be protected from light.

Identification

      A. To a portion of the powdered tablets, containing 300 mg of metronidazole, add 20 ml of diluted hydrochloric acid  (1 in 100), shake for several minutes, and filter: the ultraviolet absorption spectrum of the suitable aliquots of the filtrate in a mixture 1 volume of sulfuric acid  in 350 volumes of methanol when observed between 230 and 350 nm, exhibits a maximum at 278 nm.

      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.

Dissolution Carry out the test as described in the “Dissolution Test” (Appendix 4.24).

      Dissolution medium: 0.1 M hydrochloric acid ; 900 ml.

      Apparatus 1: 100 rpm.

      Time: 60 minutes.

      Procedure Determine the amount of C₆H₉N₃O₃ dissolved from absorbances at the maximum at about 278 nm of filtered portions of the test solution, suitably diluted with Dissolution medium , if necessary, in comparison with a standard solution having a known concentration of Metronidazole RS in the same medium (Appendix 2.2).

      Tolerances Not less than 85 per cent (Q) of the labelled amount of C₆H₉N₃O₃ is dissolved in 60 minutes.

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

      Mobile phase Prepare a mixture of 4 volumes of water and 1 volume of methanol.

      Standard preparation Dissolve an accurately weighed quantity of Metronidazole RS in Mobile phase, and dilute quantitatively and stepwise with the same solvent to obtain a solution having a known concentration of about 500 μg per ml.

      Assay preparation Transfer to a suitable size volumetric flask not less than 10 Metronidazole Tablets, whole or ground, which when diluted with methanol  will yield a solution having a known concentration of about 10 mg per ml. Add methanol, and shake by mechanical means for 30 minutes or until the Tablets are disintegrated. Dilute with methanol to volume, and allow the solution to stand until the insoluble material has settled. Pipette 5.0 ml of the clear supernatant liquid into a 100-ml volumetric flask, dilute with Mobile phase  to volume, and mix. Filter the solution.

      Chromatographic system The chromatographic procedure may be carried out using (a) a stainless steel column (15 cm × 4.6 mm) packed with octylsilane chemically bonded to totally porous microsilica particles (5 to 10 μm), (b) Mobile phase  at a flow rate of about 1 ml per minute, and (c) an ultraviolet photometer set at 254 nm.

      To determine the suitability of the chromatographic system, 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 and the symmetry factor is not more than 2.0.

      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 C₆H₉N₃O₃ in the portion of the Tablets taken, using the declared content of C₆H₉N₃O₃ in Metronidazole RS.

Other requirements Comply with the requirements described under “Tablets” (Appendix 1.16).