Co-amoxiclav Tablets
Action and use
Penicillin antibacterial + beta-lactamase inhibitor.
Definition
Co-amoxiclav Tablets contain Amoxicillin Trihydrate and either Potassium Clavulanate or Diluted Potassium Clavulanate.
Content of amoxicillin, C16H19N3O5S
90.0 to 105.0% of the stated amount.
Content of clavulanic acid, C8H9NO5
90.0 to 105.0% of the stated amount.
Identification
Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
1 volume of butan-1-ol, 2 volumes of a 0.1% w/v solution of disodium edetate in mixed phosphate buffer pH 4.0, 6 volumes of glacial acetic acid and 10 volumes of butyl acetate.
The principal spots in the chromatogram obtained with solution (1) correspond in position and colour to those in the chromatogram obtained with solution (2).
Tests
Dissolution
Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
The chromatographic procedure described under Assay may be used.
Calculate the total content of amoxicillin, C16H19N3O5S, and of clavulanic acid, C8H9NO5, in the medium from the chromatograms obtained and using the declared content of C16H19N3O5S in amoxicillin trihydrate BPCRS and the declared content of C8H8LiNO5 in lithium clavulanate EPCRS. Each mg of C8H8LiNO5 is equivalent to 0.9711 mg of C8H9NO5.
Clavulanate polymer and other fluorescent impurities
Carry out the method for fluorescence spectrophotometry, Appendix II E, using the following freshly prepared solutions.
Measure the fluorescence of the solutions using an excitation wavelength of 360 nm and an emission wavelength of 440 nm, using the phosphate buffer solution in the reference cell.
The fluorescence obtained with solution (1) is not more intense than that obtained with solution (2) (5% w/w, calculated with respect to the content of clavulanic acid).
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
Use the following gradient conditions:
Equilibrate the column with the mobile phase ratio established during system suitability. Inject freshly prepared solution (1) and immediately after the elution of the amoxicillin peak start a linear gradient elution to reach a mobile phase ratio A:B of 0:100 over 25 minutes. Continue the chromatography with mobile phase B for a further 15 minutes. Equilibrate the column for 15 minutes with the starting mobile phase ratio established during system suitability before the next injection.
Inject mobile phase A using the same elution gradient to obtain a blank.
Equilibrate the column with a mobile phase ratio A:B of 92:8. The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks due to amoxicillin and cefadroxil is at least 2.0. If necessary adjust the ratio A:B of the mobile phase.
In the chromatogram obtained with solution (1):
the area of any peak with a retention time relative to amoxicillin of about 4.1 (amoxicillin dimer) is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (2%);
the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%).
Disregard any peak corresponding to the principal peak in the chromatogram obtained with solution (4).
Assay
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
5 volumes of methanol and 95 volumes of a 0.78% w/v solution of sodium dihydrogen orthophosphate monohydrate, adjusted to pH 4.4 with orthophosphoric acid.
The assay is not valid unless, in the chromatogram obtained with solution (2), the resolution factor between the peaks due to amoxicillin and lithium clavulanate is at least 3.5 and the symmetry factor of the peak due to lithium clavulanate is at most 1.5.
Calculate the content of C16H19N3O5S and of C8H9NO5 in the tablets using the declared content of C16H19N3O5S in amoxicillin trihydrate BPCRS and the declared content of C8H8LiNO5 in lithium clavulanate EPCRS. Each mg of C8H8LiNO5 is equivalent to 0.9711 mg of C8H9NO5.
Storage
Co-amoxiclav Tablets should be protected from light and stored in an airtight container.
Labelling
The quantity of Amoxicillin Trihydrate is stated in terms of the equivalent amount of amoxicillin, and the quantity of Potassium Clavulanate is stated in terms of the equivalent amount of clavulanic acid.
The label states that the preparation contains a penicillin.