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Category Antibacterial (second-generation cephalosporin).

Cefuroxime Axetil Tablets contain the equivalent of not less than 90.0 per cent and not more than 110.0 per cent of the labelled amount of C₁₆H₁₆N₄O₈S.

Strengths available 125, 250 and 500 mg (base).

Dose Adults: 250 or 500 mg twice daily.
          Children: 125 or 250 twice daily.

Contra-indication See under Cefuroxime Axetil, p 52.

Warning It may cause transient increase in serum aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) and alkaline phosphatase concentrations and jaundice.
          See also under Cephalexin, p. 58.

Additional information See under Cephalexin, p. 59.

Packaging and storage Cefuroxime Axetil Tablets shall be kept in tightly closed containers.

Labelling The label on the container states (1) the quantity equivalent to the amount of cefuroxime; (2) whether it is amorphous or crystalline.

Identification
          A. Extract a quantity of the powdered tablets containing the equivalent of 100 mg of cefuroxime with 5 ml of dichloromethane, filter and evaporate the filtrate to dryness: the infrared absorbtion spectrum of the residue is concordant with the spectrum obtained from Cefuroxime Axetil RS (Appendix 2.1) or with the reference spectrum Cefuroxime Axetil.
          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 substances Carry out the test as described under Assay using Standard preparation, Assay preparation 1, Assay preparation 2, and Assay preparation 3. Prepare the solutions immediately before use.
     Calculate the percentage content of related substances from the areas in chromatogram obtained from the Assay preparation 1 by normalization.
     Limits
          E-isomers The sum of the areas of the pair of peaks corresponding to the E-isomers in the Assay preparation 3 is not more than 1.5 per cent.
          Δ³-isomers The sum of the areas of the pair of peaks corresponding to the Δ³-isomers in the Assay preparation 2 is not more than 2.0 per cent.
          Any impurity The area of any other secondary peak is not more than 1.0 per cent.

Dissolution Carry out the test as described in the “Dissolution Test” (Appendix 4.24).
          Dissolution medium: 0.07 M hydrochloric acid; 900 ml.
          Apparatus 2: 55 rpm.
          Time: 15 and 45 minutes.
          Procedure Determine the amount of C₁₆H₁₆N₄O₈S dissolved from absorbances at the maximum at about 278 nm of a filtered portion of the test solution, suitably diluted with Dissolution medium, if necessary, in com-parison with a standard solution having a known concentration of Cefuroxime Axetil RS equivalent to about 10 to 20 μg of cefuroxime per ml in the same medium (Appendix 2.2).
          Tolerances Not less than 60 per cent (Q) of the labelled amount of C₁₆H₁₆N₄O₈S is dissolved in 15 minutes, and not less than 75 per cent (Q) is dissolved in 45 minutes, except that where Tablets are labelled to contain the equivalent of 500 mg of cefuroxime, not less than 50 per cent (Q) of the labelled amount of C₁₆H₁₆N₄O₈S is dissolved in 15 minutes and not less than 70 per cent (Q) is dissolved in 45 minutes.

Assay Carry out the determination as described in the “High-pressure Liquid Chromatography” (Appendix 3.5). (Note All solutions containing cefuroxime axetil, if not to be used for immediate analysis, should be stored in the dark at a temperature between 2º and 8º before analysis.)
          Mobile phase Prepare a mixture of 38 volumes of methanol and 62 volumes of a 0.2 M ammonium dihydrogenphosphate. Make adjustments if necessary.
          Standard preparation Dissolve an accurately weighed quantity of Cefuroxime Axetil RS in Mobile phase and dilute quantitatively to obtain a solution having a known concentration of about 300 μg per ml.
          Assay preparation 1 Disperse 10 Cefuroxime Axetil Tablets in 0.2 M ammonium dihydrogenphosphate, previously adjusted to pH 2.4 with phosphoric acid, using about 10 ml per g of the stated content of cefuroxime, accurately measured. Immediately add sufficient methanol to produce a solution containing the equivalent of about 0.5 per cent w/v of cefuroxime and shake vigorously. Filter and dilute a quantity of the filtrate with sufficient of Mobile phase to produce a solution containing the equivalent of about 0.025 per cent w/v of cefuroxime.
          Assay preparation 2​ Heat a quantity of Assay preparation at 60^º for 1 hour or until sufficient impurities (Δ³-isomers) have been generated. Assay preparation 3 Expose a quantity of Assay preparation to ultraviolet light at 254 nm for 24 hours or until sufficient impurities (E-isomers) have been generated.
          Assay preparation 3  Expose a quantity of Assay preparation to ultraviolet light at 254 nm for 24 hours or until sufficient impurities (E-isomers) have been generated. 
          Chromatographic system​ The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4.6 mm) packed with trimethyl group chemically bonded to porous silica microparticles (5 μm), (b) Mobile phase at a flow rate of about 1.2 ml per minute, and (c) an ultraviolet photometer set at 278 nm.
          To determine the suitability of the chromatographic system, chromatograph Assay preparation 2, and record the peak responses as directed under Procedure: the resolution factor between cefuroxime axetil diastereoisomer A and cefuroxime axetil Δ³-isomer peaks is not less than 1.5. 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 resolution factor between cefuroxime axetil diastereoisomer A and B peaks is not less than 1.5. The relative retention times are about 0.9 for cefuroxime axetil diastereoisomer B, 1.2 for cefuroxime axetil Δ³-isomer, 1.7 and 2.1 for Eisomers, and 1.0 for cefuroxime axetil diastereoisomer A.
          Procedure​ Separately inject equal volumes (about 20 μl) of Standard preparation and Assay preparation 1 into the chromatograph, record the chromatograms, and measure the responses for the major peaks.
          Calculation Calculate the content of C₁₆H₁₆N₄O₈S in the portion of the Tablets taken, using the declared content of C₂₀H₂₂N₄O₁₀S in Cefuroxime Axetil RS. Each mg of C₂₀H₂₂N₄O₁₀S is equivalent to 0.8313 mg of C₁₆H₁₆N₄O₈S.

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