Cefadroxil Oral Suspension

Cephalosporin antibacterial.

Cefadroxil Oral Suspension is a suspension of Cefadroxil Monohydrate 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.

The dry ingredients should be stored at a temperature not exceeding 30°.

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 110.0% 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 90.0% of the stated amount.

A. Carry out the method for thin-layer chromatography, Appendix III A, using a TLC silica gel plate (Merck silica gel 60 plates are suitable) and a mixture of 3 volumes of a 6.7% w/v solution of ninhydrin in acetone, 80 volumes of a 0.1m solution of disodium hydrogen orthophosphate and 120 volumes of a 0.1m solution of citric acid as the mobile phase. Impregnate the plate by development with a 5% v/v solution of n-tetradecane in hexane. Allow the solvent to evaporate and carry out the chromatography in the same direction as the impregnation. Apply separately to the plate 20 µL of each of the following solutions. For solution (1) dilute a volume of the oral suspension containing the equivalent of 0.2 g of anhydrous cefadroxil to 100 mL with water, filter and use the filtrate. Solution (2) contains 0.2% w/v of cefadroxil BPCRS in water. After removal of the plate, allow it to dry in air, spray with a 0.2% w/v solution of ninhydrin in absolute ethanol, heat the plate at 110° for 10 minutes and allow to cool. The principal spot in the chromatogram obtained with solution (1) is similar in position and size to that in the chromatogram obtained with solution (2).

B. In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).

pH, 4.5 to 6.0, Appendix V L.

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) dilute a volume of the oral suspension with sufficient of mobile phase A to produce a solution containing the equivalent of 0.1% w/v of anhydrous cefadroxil, mix, stir magnetically for 10 minutes, filter through a 0.45-µm filter and use the filtrate. Solution (2) contains 0.001% w/v of cefadroxil BPCRS in mobile phase A. Solution (3) contains 0.001% w/v of d-α-(4-hydroxyphenyl)glycine BPCRS (cefadroxil impurity A) in the mobile phase. Solution (4) contains 0.001% w/v of 7-aminodesacetoxycephalosporanic acid BPCRS (cefadroxil impurity B) in the mobile phase.

The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4 mm) packed with octadecylsilyl silica gel for chromatography (10 µm) (Lichrosorb RP-18 is suitable), (b) as mobile phases A and B with a flow rate of 1 mL per minute the solutions described below and (c) a detection wavelength of 254 nm.

Mobile phase A  Dissolve 5.44 g of potassium dihydrogen orthophosphate in 2000 mL of water and adjust the pH, if necessary, to 5.0 with a 1% w/v solution of potassium hydroxide.

Mobile phase B  Add 400 mL of acetonitrile to 600 mL of mobile phase A and adjust the pH, if necessary to 5.0 with a 2% v/v solution of orthophosphoric acid.

Inject 20 µL of each solution and record the chromatograms under the following conditions. Elute initially with mobile phase A. After 5 minutes, use linear gradient elution increasing the concentration of mobile phase B to 32% after 35 minutes. Elute isocratically for 25 minutes with a mixture of 32% of mobile phase B and 68% of mobile phase A. Carry out a linear gradient elution for 1 minute to 100% of mobile phase A and elute for a further 9 minutes with mobile phase A.

When the chromatograms are recorded under the conditions described above the retention time of cefadroxil is 14 to 20 minutes. If necessary, adjust the proportion of mobile phase A to mobile phase B to achieve the stated retention time.

The test is not valid unless the column efficiency, determined on the peak due to cefadroxil in the chromatogram obtained with solution (2), is at least 2000 theoretical plates per metre and the symmetry factor of the principal peak is at most 1.5.

Inject solution (2) five times. The test is not valid unless the relative standard deviation of the area of the principal peak is at most 2.0%.

In the chromatogram obtained with solution (1) the area of any peak corresponding to cefadroxil impurity A is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (1%), the area of any peak corresponding to cefadroxil impurity B is not greater than the area of the principal peak in the chromatogram obtained with solution (4) (1%) and 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 with an area less than 0.1 times the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a weighed quantity of the oral suspension containing the equivalent of 0.25 g of anhydrous cefadroxil with 250 mL of a phosphate buffer prepared by dissolving 13.6 g of potassium dihydrogen orthophosphate in sufficient water to produce 2000 mL and adjusting the pH, if necessary, to 5.0 with 10m potassium hydroxide for 5 minutes; filter and use the filtrate. Solution (2) contains 0.1% w/v of cefadroxil BPCRS in the buffer solution. Solution (3) contains 0.005% w/v of cefadroxil BPCRS and 0.05% w/v of amoxicillin trihydrate BPCRS in the buffer solution.

The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm or 10 µm) (Hypersil ODS is suitable), (b) as the mobile phase at a flow rate of 1.0 mL per minute a mixture of 4 volumes of acetonitrile and 96 volumes of a 0.272% w/v solution of potassium dihydrogen orthophosphate and (c) a detection wavelength of 254 nm.

The assay is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks corresponding to cefadroxil and amoxicillin is at least 5.0. If necessary, adjust the acetonitrile content in the mobile phase.

Determine the weight per mL of the oral suspension, Appendix V G, and calculate the content of C₁₆H₁₇N₃O₅S, weight in volume, using the declared content of C₁₆H₁₇N₃O₅S in cefadroxil BPCRS.

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.

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

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