Cefuroxime Axetil Tablets

General Notices

Action and use

Cephalosporin antibacterial.

Definition

Cefuroxime Axetil Tablets contain Cefuroxime Axetil. They may be coated.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of cefuroxime, C16H16N4O8S

92.5 to 105.0% of the stated amount.

Identification

A. Extract a quantity of the powdered tablets containing the equivalent of 0.1 g of cefuroxime with 5 mL of dichloromethane, filter and evaporate the filtrate to dryness. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of cefuroxime axetil (RS 047).
B. In the Assay, the retention times of the principal peaks in the chromatogram obtained with solution (1) correspond to those of the peaks due to diastereoisomers A and B of cefuroxime axetil in the chromatogram obtained with solution (4).

Tests

Related substances

Carry out the method for liquid chromatography, Appendix III D, using solutions (1) to (3) described under Assay.

chromatographic conditions

The chromatographic conditions described under Assay may be used.

system suitability

The requirements stated under Assay apply.

limits

In the chromatogram obtained with solution (1):

the sum of the areas of the pair of peaks corresponding to the E-isomers in the chromatogram obtained with solution (3) is not greater than 1.5% by normalisation;

the sum of the areas of any peaks corresponding to the Δ3-isomers in the chromatogram obtained with solution (2) is not greater than 2.0% by normalisation;

the area of any other secondary peak is not greater than 1.0% by normalisation.

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.

test conditions
(a) Use Apparatus 2, rotating the paddle at 50 revolutions per minute.
(b) Use 900 mL of 0.1m hydrochloric acid, at a temperature of 37°, as the medium.
procedure
(1) After 45 minutes withdraw a 10 mL sample of the medium and measure the absorbance of the filtered sample, diluted with 0.1m hydrochloric acid to produce a solution expected to contain the equivalent of 10 to 20 µg of cefuroxime per mL, at the maximum at 278 nm, Appendix II B, using 0.1m hydrochloric acid in the reference cell.
(2) Measure the absorbance of a solution of cefuroxime axetil BPCRS in 0.1m hydrochloric acid containing the equivalent of 10 to 20 µg of cefuroxime per mL and using 0.1m hydrochloric acid in the reference cell.
determination of content

Calculate the total content of cefuroxime axetil, C16H16N4O8S, in the medium from the absorbances obtained and using the declared content of C20H22N4O10S in cefuroxime axetil BPCRS. Each mg of C20H22N4O10S is equivalent to 0.8313 mg of C16H16N4O8S.

Assay

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. The solutions should be used immediately or stored in the dark at a temperature of 2° to 8° before analysis.

(1) Disperse 5 tablets in 0.2m ammonium dihydrogen orthophosphate, previously adjusted to pH 2.4 with orthophosphoric acid, using 10 mL per g of the stated content of cefuroxime. Immediately add 375 mL of methanol and shake vigorously for 10 minutes. Mix with the aid of ultrasound for a further 10 minutes and add sufficient methanol to produce 500 mL. Centrifuge a portion of the solution for at least 5 minutes at 2500 rpm and then dilute a quantity of the supernatant liquid with sufficient of the mobile phase to produce a solution containing the equivalent of 0.025% w/v of cefuroxime.
(2) Heat a quantity of solution (1) at 60° for 1 hour or until sufficient impurities (Δ3-isomers) have been generated.
(3) Expose a quantity of solution (1) to ultraviolet light (254 nm) for 24 hours or until sufficient impurities (E-isomers) have been generated.
(4) 0.03% w/v of cefuroxime axetil BPCRS in the mobile phase. 
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with particles of silica (5 µm) the surface of which has been modified by chemically-bonded trimethylsilyl groups (Hypersil SAS is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 278 nm.
(f) Inject 20 µL of each solution.
mobile phase

38 volumes of methanol and 62 volumes of 0.2m ammonium dihydrogen orthophosphate.

When the chromatograms are recorded under the prescribed conditions the retention times relative to cefuroxime axetil diastereoisomer A are approximately 0.9 for cefuroxime axetil diastereoisomer B, 1.2 for the cefuroxime axetil Δ3-isomers and 1.7 and 2.1 for the E-isomers.

system suitability

The Assay is not valid unless:

in the chromatogram obtained with solution (2), the resolution factor between the peaks due to cefuroxime axetil diastereoisomer A and the cefuroxime axetil Δ3-isomer is at least 1.5 (if necessary, adjust the composition of the mobile phase);

in the chromatogram obtained with solution (4), the resolution factor between the peaks corresponding to cefuroxime axetil diastereoisomers A and B is at least 1.5 (if necessary, adjust the composition of the mobile phase).

determination of content

Calculate the content of C16H16N4O8S as the sum of the areas of the two peaks corresponding to diastereoisomers A and B of cefuroxime axetil and using the declared content of C20H22N4O10S in cefuroxime axetil BPCRS. Each mg of C20H22N4O10S is equivalent to 0.8313 mg of C16H16N4O8S.

Labelling

The quantity of active ingredient is stated in terms of the equivalent amount of cefuroxime.