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Category Antibacterial. 

      Nalidixic Acid Tablets contain not less than 95.0 per cent and not more than 105.0 per cent of the labelled amount of C₁₂H₁₂N₂O₃.

Strengths available 250, 500 and 1000 mg.

Dose Adults: 1 g four times daily for 1 to 2 weeks. Children and infants 3 months of age and over: 55 mg per kg of body weight daily, administered in four equally divided doses.

Contra-indication; Warning; Precaution See under Norfloxacin, p. 133.

Additional information

      1. The drug should not be used in the treatment of systemic infections where high serum and tissue concentrations of antibacterial agents are desirable.

      2. To minimize the development of bacterial resistance, patients should be carefully instructed not to omit doses of the drug, especially during the first few days of therapy.

      See also under Norfloxacin, p. 133.

Packaging and storage Nalidixic acid Tablets shall be kept in tightly closed containers, protected from light.

Identification To a portion of the powdered tablets, containing 1 g of nalidixic acid, add 50 ml of chloroform, shake for 15 minutes, filter, and evaporate the filtrate to dryness. The residue, after drying at 105º, complies with the following tests.

      A. The infrared absorption spectrum of the residue is concordant with the spectrum obtained from Nalidixic Acid RS (Appendix 2.1) or with the reference spectrum of Nalidixic Acid.

      B. The ultraviolet absorption spectrum of a 0.0008 per cent w/v solution of the residue in 0.1 M sodium hydroxide, when observed between 230 and 350 nm, exhibits two maxima at 258 nm and 334 nm (Appendix 2.2).

      C. 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.

      D. The residue melts at about 228º (Appendix 4.3).

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

      Dissolution medium: pH 8.60 buffer, prepared by mixing 23 volumes of 0.2 M sodium hydroxide with 25 volumes of 0.2 M potassium dihydrogenphosphate and 20 volumes of methanol, cooling, mixing with water to obtain 100 volumes of solution, adjusting, if necessary, by the addition of 1 M sodium hydroxide to a pH of 8.60±0.05. The initial volume for the test is 900 ml.

      Apparatus 2: 60 rpm.

      Time: 30 minutes.

      Procedure Determine the amount of C₁₂H₁₂N₂O₃ dissolved from absorbances at the maximum at about 258 nm of filtered portion of the test solution, suitably diluted with 0.01 M sodium hydroxide, if necessary, in comparison with a standard solution having a known concentration of Nalidixic Acid RS in 0.01 M sodium hydroxide, using as the blank a mixture of Dissolution medium and 0.01 M sodium hydroxide in the same proportions as present in the test solution.

      Tolerances Not less than 80 per cent (Q) of the labelled amount of C₁₂H₁₂N₂O₃ is dissolved in 30 minutes.

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

      Mobile phase Prepare a solution of 784 mg of dipotassium hydrogenphosphate in 325 ml of water. To this solution add a solution of 2.62 g of hexadecyltrimethylammonium bromide in 350 ml of methanol. To the combined solution add 325 ml of methanol, mix and filter. This solution has an apparent pH of about 10. Make adjustments if necessary.

      Internal standard solution Prepare a solution of sulfanilic acid in Mobile phase containing 800 μg per ml.

      Standard preparation Dissolve an accurately weighed quantity of Nalidixic Acid RS in methanol to obtain a solution having a known concentration of about 180 μg per ml. Transfer 5.0 ml of this solution and 1.0 ml of Internal standard solution to a 25-ml volumetric flask, dilute with methanol to volume and mix.

      Assay preparation Weigh and finely powder not less than 20 Nalidixic Acid Tablets. Transfer an accurately weighed portion of the powder containing about 150 mg of nalidixic acid, to a 500-ml volumetric flask. Add 400 ml of methanol and sonicate for 30 minutes. Shake by mechanical means for 30 minutes, sonicate again for 30 minutes, dilute with methanol to volume, mix, and filter. Transfer 3.0 ml of the clear filtrate and 1.0 ml of Internal standard solution to a 25-ml volumetric flask, dilute with methanol to volume and mix.

      Procedure Separately inject equal volumes (about 20 μl) of Standard preparation and Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. 

      Chromatographic system The chromatographic procedure may be carried out using (a) a stainless steel column (30 cm × 3.9 mm) packed with octadecylsilane chemically bonded to porous silica or ceramic microparticles (3 to 10 μm), (b) Mobile phase at a flow rate of about 1.5 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 retention times are 1.0 for sulfanilic acid and 1.4 for nalidixic acid, the resolution factor between sulfanilic acid and nalidixic acid peaks is more than 1, and the relative standard deviation for replicate injections is not more than 2.0 per cent.

      Calculation Calculate the content of C₁₂H₁₂N₂O₃ in the portion of the Tablets taken, using the declared content of C₁₂H₁₂N₂O₃ in Nalidixic Acid RS.

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