Co-amoxiclav Oral Suspension

Amoxicillin and Potassium Clavulanate Oral Suspension

Penicillin antibacterial + beta-lactamase inhibitor.

Co-amoxiclav Oral Suspension is a suspension containing Amoxicillin Trihydrate and either Potassium Clavulanate or Diluted Potassium Clavulanate in a suitable flavoured vehicle. It is prepared by dispersing the dry ingredients in the specified volume of Water just before issue for use.

The dry ingredients comply with the requirements for Powders and Granules for Oral Solutions and Oral Suspensions stated under Oral Liquids.

For the following tests prepare the oral suspension as directed on the label. The suspension, examined immediately after preparation unless otherwise indicated, complies with the requirements stated under Oral Liquids and with the following requirements.

When freshly constituted, not more than 120.0% of the stated amount. When stored at the temperature and for the period stated on the label during which the oral suspension may be expected to be satisfactory for use, not less than 80.0% of the stated amount.

When freshly constituted, not more than 120.0% of the stated amount. When stored at the temperature and for the period stated on the label during which the oral suspension may be expected to be satisfactory for use, not less than 80.0% of the stated amount.

Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.

(1) Disperse, with shaking, a quantity of the oral suspension containing the equivalent of 0.4 g of clavulanic acid in 100 mL of a mixture of 4 volumes of methanol and 6 volumes of 0.1m mixed phosphate buffer pH 7.0 and filter.

(2) 0.4% w/v of lithium clavulanate EPCRS and 0.8% w/v of amoxicillin trihydrate BPCRS in a mixture of 4 volumes of methanol and 6 volumes of 0.1m mixed phosphate buffer pH 7.0.

(a) Use a silica gel F₂₅₄ precoated plate (Merck silica gel 60 F₂₅₄ plates are suitable). Impregnate the plate by spraying it with a 0.1% w/v solution of disodium edetate in mixed phosphate buffer pH 4.0 and allow to dry overnight. Activate the plate by heating at 105° for 1 hour just prior to use.

(b) Use the mobile phase described below.

(c) Apply 1 µL of each solution.

(d) Develop the plate to 15 cm.

(e) After removal of the plate, dry in air and examine under ultraviolet light (254 nm).

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).

pH of a solution containing the equivalent of 2.5% w/v of amoxicillin, 4.0 to 7.0, Appendix V L.

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Disperse, with shaking, a quantity of the oral suspension containing the equivalent of 30 mg of amoxicillin in 15 mL of mobile phase A. Add sufficient mobile phase A to produce 20 mL and filter through a 0.45-µm membrane filter.

(2) Dilute 1 volume of solution (1) to 100 volumes with mobile phase A.

(3) 0.0004% w/v of cefadroxil BPCRS and 0.003% w/v of amoxicillin trihydrate BPCRS in mobile phase A.

(4) 0.075% w/v of lithium clavulanate EPCRS in mobile phase A.

(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Hypersil ODS is suitable).

(b) Use gradient elution and the mobile phase described below.

(c) Use a flow rate of 1 mL per minute.

(d) Use an ambient column temperature.

(e) Use a detection wavelength of 254 nm.

(f) Inject 50 µL of each solution.

Mobile phase A  1 volume of acetonitrile and 99 volumes of a pH 5.0 buffer solution prepared in the following manner. To 250 mL of 0.2m potassium dihydrogen orthophosphate add 2m sodium hydroxide until the pH reaches 5.0 and then add sufficient water to produce 1000 mL.

Mobile phase B  20 volumes of acetonitrile and 80 volumes of the pH 5.0 buffer solution.

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) and any peaks due to excipients.

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Disperse, with shaking, a quantity of the oral suspension containing the equivalent of 0.25 g of amoxicillin in 400 mL of water, add sufficient water to produce 500 mL, mix and filter.

(2) 0.05% w/v of amoxicillin trihydrate BPCRS and 0.02% w/v of lithium clavulanate EPCRS in water.

(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Hypersil ODS 5 µm is suitable).

(b) Use isocratic elution and the mobile phase described below.

(c) Use a flow rate of 2 mL per minute.

(d) Use an ambient column temperature.

(e) Use a detection wavelength of 220 nm.

(f) Inject 20 µL of each solution.

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.

Determine the weight per mL of the oral suspension, Appendix V G, and calculate the content of C₁₆H₁₉N₃O₅S and of C₈H₉NO₅, weight in volume, 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.

Repeat the procedure using a portion of the oral suspension that has been stored at the temperature and for the period stated on the label during which it may be expected to be satisfactory for use.

The Oral Suspension should be kept at the temperature and used within the period stated on the label.

The label states the quantity of Amoxicillin Trihydrate, in terms of the equivalent amount of amoxicillin, and the quantity of Potassium Clavulanate, in terms of the equivalent amount of clavulanic acid.

The label states that the preparation contains penicillin.