Cefalexin Capsules

General Notices

Action and use

Cephalosporin antibacterial.

Definition

Cefalexin Capsules contain Cefalexin Monohydrate.

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

Content of anhydrous cefalexin, C16H17N3O4S

92.5 to 110.0% of the stated amount.

Identification

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 the following solutions in a mixture of equal volumes of methanol and 0.067m mixed phosphate buffer pH 7.0.
(1) Shake a quantity of the contents of the capsules containing the equivalent of 0.2 g of anhydrous cefalexin with 25 mL, dilute to 50 mL, filter and use the filtrate.
(2) 0.4% w/v of cefalexin BPCRS.
(3) 0.4% w/v of each of cefalexin BPCRS and cefradine BPCRS.
chromatographic conditions
(a) Use as the coating silanised silica gel HF254.
(b) Use the mobile phase as described below.
(c) Apply 1 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, allow it to dry and examine under ultraviolet light (254 nm).
mobile phase

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.

system suitability

The test is not valid unless the chromatogram obtained with solution (3) shows two clearly separated spots.

confirmation

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).

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.

Tests

Disintegration

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

Related substances

Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions in 2m hydrochloric acid.

(1) Shake a quantity of the contents of the capsules containing the equivalent of 0.25 g of anhydrous cefalexin with 10 mL, filter and use the filtrate.
(2) Dilute 1 volume of solution (1) to 100 volumes.
(3) 0.025% w/v of 7-aminodesacetoxycephalosporanic acid BPCRS.
(4) 0.025% w/v of dl-phenylglycine.
(5) 2.5% w/v of cefalexin BPCRS and 0.025% w/v of each of 7-aminodesacetoxycephalosporanic acid BPCRS and dl-phenylglycine.
chromatographic conditions
(a) Use a silica gel HF precoated plate (Analtech plates are suitable). 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.
(b) Use the mobile phase as described below.
(c) Apply 5 µL of each solution.
(d) Develop the plate to 15 cm.
(e) 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.
mobile phase

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.

system suitability

The test is not valid unless the chromatogram obtained with solution (5) shows three clearly separated spots.

limits

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%);

any other secondary spot is not more intense than the spot in the chromatogram obtained with solution (2) (1%).

Assay

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

(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, filter and dilute 25 mL of the filtrate to 50 mL.
(2) 0.05% w/v of cefalexin BPCRS.
(3) 0.01% w/v of each of cefalexin BPCRS and cefradine BPCRS.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Nucleosil C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 254 nm.
(f) Inject 20 µL of each solution.
mobile phase

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.

system suitability

The Assay is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks corresponding to cefalexin and cefradine is at least 4.0; if necessary, adjust the acetonitrile content of the mobile phase.

Inject solution (2) six times. The Assay is not valid unless the relative standard deviation of the area of the principal peak is at most 1.0%.

determination of content

Calculate the content of C16H17N3O4S in the capsules using the declared content of C16H17N3O4S in cefalexin BPCRS.

Storage

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

Labelling

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