Cefalexin Capsules

Cephalosporin antibacterial.

Cefalexin Capsules contain Cefalexin Monohydrate.

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

92.5 to 110.0% of the stated amount.

A. Shake a quantity of the contents of the capsules containing the equivalent of 0.5 g of anhydrous cefalexin with 1 mL of water and 1.4 mL of 1m hydrochloric acid, filter and wash the filter with 1 mL of water. Add slowly to the filtrate a saturated solution of sodium acetate until precipitation occurs. Add 5 mL of methanol, filter, wash the precipitate with two 1 mL quantities of methanol and dry the residue at a pressure not exceeding 0.7 kPa. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with the reference spectrum of cefalexin (RS 049). Retain the dried residue for use in test C.

B. Carry out the method for thin-layer chromatography, Appendix III A, using silanised silica gel HF₂₅₄ as the coating substance and a mixture of 15 volumes of acetone and 85 volumes of a 15.4% w/v solution of ammonium acetate, previously adjusted to pH 6.2 with 5m acetic acid as the mobile phase. Apply separately to the plate 1 µL of each of the following solutions. For solution (1) shake a quantity of the contents of the capsules containing the equivalent of 0.2 g of anhydrous cefalexin with 25 mL of a mixture of equal volumes of methanol and 0.067m mixed phosphate buffer pH 7.0, dilute to 50 mL with the same solvent mixture, filter and use the filtrate. Solution (2) contains 0.4% w/v of cefalexin BPCRS in a mixture of equal volumes of methanol and 0.067m mixed phosphate buffer pH 7.0. Solution (3) contains 0.4% w/v of cefalexin BPCRS and 0.4% w/v of cefradine BPCRS in a mixture of equal volumes of methanol and 0.067m mixed phosphate buffer pH 7.0. After removal of the plate, allow it to dry and examine under ultraviolet light (254 nm). 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). The test is not valid unless the chromatogram obtained with solution (3) shows two clearly separated spots.

C. Mix 20 mg of the dried residue obtained in test A with 0.25 mL of a 1% v/v solution of glacial acetic acid and add 0.1 mL of a 1% w/v solution of copper(ii) sulfate and 0.1 mL of 2m sodium hydroxide. An olive-green colour is produced.

Maximum time, 15 minutes, using a 0.6% v/v solution of hydrochloric acid in place of water, Appendix XII A1.

Carry out the method for thin-layer chromatography, Appendix III A, using a silica gel HF precoated plate (Analtech plates are suitable) and a mixture of 3 volumes of acetone, 80 volumes of a 7.2% w/v solution of disodium hydrogen orthophosphate and 120 volumes of a 2.1% w/v 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 5 µL of each of the following solutions. For solution (1) shake a quantity of the contents of the capsules containing the equivalent of 0.25 g of anhydrous cefalexin with 10 mL of 2m hydrochloric acid, filter and use the filtrate. For solution (2) dilute 1 volume of solution (1) to 100 volumes with 2m hydrochloric acid. Solution (3) contains 0.025% w/v of 7-aminodesacetoxycephalosporanic acid BPCRS in 2m hydrochloric acid. Solution (4) contains 0.025% w/v of dl-phenylglycine in 2m hydrochloric acid. Solution (5) contains 2.5% w/v of cefalexin BPCRS and 0.025% w/v of each of 7-aminodesacetoxycephalosporanic acid BPCRS and dl-phenylglycine in 2m hydrochloric acid. After removal of the plate, dry it at 90° for 3 minutes, spray the hot plate with a 0.1% w/v solution of ninhydrin in the mobile phase, heat the plate at 90° for 15 minutes and allow to cool. In the chromatogram obtained with solution (1) any spot corresponding to 7-aminodesacetoxycephalosporanic acid is not more intense than the spot in the chromatogram obtained with solution (3) (1%), any spot corresponding to DL-phenylglycine is not more intense than the spot in the chromatogram obtained with solution (4) (1%) and any other secondary spot is not more intense than the spot in the chromatogram obtained with solution (2) (1%). The test is not valid unless the chromatogram obtained with solution (5) shows three clearly separated spots.

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of the powdered, mixed contents of 20 capsules containing the equivalent of 0.25 g of anhydrous cefalexin with 100 mL of water for 30 minutes, add sufficient water to produce 250 mL and filter. Dilute 25 mL of the filtrate to 50 mL with water. Solution (2) contains 0.05% w/v of cefalexin BPCRS in water. Solution (3) contains 0.01% w/v each of cefalexin BPCRS and cefradine BPCRS in water.

The chromatographic procedure may be carried out using (a) a column (25 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Nucleosil C18 is suitable), (b) a mixture of 2 volumes of methanol, 5 volumes of acetonitrile, 10 volumes of a 1.36% w/v solution of potassium dihydrogen orthophosphate and 83 volumes of water as the mobile phase with a flow rate of 1.5 mL per minute and (c) a detection wavelength of 254 nm. Adjust the sensitivity so that the height of the peaks in the chromatogram obtained with solution (3) is at least half the full-scale deflection on the chart recorder.

The assay is not valid unless the resolution factor between the peaks corresponding to cephalexin and cephradine in the chromatogram obtained with solution (3) is at least 4; if necessary adjust the acetonitrile content of the mobile phase. Make six injections of solution (2); the assay is not valid if the relative standard deviation for the peak area of cephalexin is greater than 1.0%.

Inject solutions (1) and (2) alternately and calculate the percentage content of C₁₆H₁₇N₃O₄S from the declared content of C₁₆H₁₇N₃O₄S in cefalexin BPCRS.

Cefalexin Capsules should be stored at a temperature not exceeding 30°.

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