Cefadroxil Capsules

General Notices

Action and use

Cephalosporin antibacterial.

Definition

Cefadroxil Capsules contain Cefadroxil Monohydrate.

The capsules comply with the requirements stated under Capsules and with the following requirements.

Content of anhydrous cefadroxil, C₁₆H₁₇N₃O₅S

92.5 to 107.5% of the stated amount.

Identification

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) stir a quantity of the contents of the capsules containing the equivalent of 0.2 g of anhydrous cefadroxil with 100 mL of 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).

Tests

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, using as the medium 900 mL of water and rotating the basket at 100 revolutions per minute. Withdraw a sample of 10 mL of the medium and filter. Measure the absorbance of the filtered medium, diluted if necessary with water, at the maximum at 263 nm using water in the reference cell, Appendix II B. Calculate the total content of anhydrous cefadroxil, C₁₆H₁₇N₃O₅S, in the medium from the absorbance obtained from a 0.003% w/v solution of cefadroxil BPCRS in water and using the declared content of C₁₆H₁₇N₃O₅S in cefadroxil BPCRS.

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following freshly prepared solutions. For solution (1) add 50 mL of the mobile phase to a quantity of the contents of the capsules containing the equivalent of 0.5 g of anhydrous cefadroxil, mix, stir magnetically for 10 minutes, filter and use the filtrate. Solution (2) contains 0.01% w/v of cefadroxil BPCRS in the mobile phase. Solution (3) contains 0.01% w/v of d-α-(4-hydroxyphenyl)glycine BPCRS (cefadroxil impurity A) in the mobile phase. Solution (4) contains 0.01% 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 (30 cm × 3.9 mm) packed with end-capped octadecylsilyl silica gel for chromatography (10 µm) (µBondapak C18 is suitable), (b) as the mobile phase with a flow rate of 1 mL per minute a solution prepared as described below and (c) a detection wavelength of 254 nm. For the mobile phase add 200 mL of 1m potassium hydroxide, 40 mL of 0.4m tetrabutylammonium hydroxide and 80 mL of methanol to 1600 mL of water, mix, add sufficient water to produce 2000 mL and adjust the pH to 7.0, if necessary, with orthophosphoric acid. For solution (1) allow the chromatography to proceed for 6 times the retention time of the principal peak.

When the chromatograms are recorded under the conditions described above the retention time of cefadroxil is 8 to 12 minutes. If necessary, adjust the composition of the mobile phase (increasing the methanol content decreases the retention time, decreasing the methanol content increases the 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 1500 theoretical plates per metre and the symmetry factor of the principal peak is at most 1.6.

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%).

Water

The contents of the capsules contain not more than 7.0% w/w of water, Appendix IX C. Use 0.5 g.

Assay

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of the mixed contents of 20 capsules containing the equivalent of 0.2 g of anhydrous cefadroxil with 150 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. Add sufficient of the buffer solution to produce 200 mL and filter. 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.

Calculate the content of C₁₆H₁₇N₃O₅S in the capsules using the declared content of C₁₆H₁₇N₃O₅S in cefadroxil BPCRS.

Labelling

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