Gastro-resistant Erythromycin Tablets

General Notices

Erythromycin Tablets

Action and use

Macrolide antibacterial.

Definition

Gastro-resistant Erythromycin Tablets contain Erythromycin. They are made gastro-resistant by enteric-coating or by other means.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of erythromycins, calculated as the sum of erythromycin A (C37H67NO13), erythromycin B (C37H67NO12) and erythromycin C (C36H65NO13)

90.0 to 110.0% of the stated amount of Erythromycin.

Identification

A. Shake a quantity of the powdered tablets containing 0.1 g of Erythromycin with 5 mL of dichloromethane, decolourise, if necessary, with activated charcoal, filter and evaporate the filtrate to dryness. The infrared absorption spectrum of the residue, Appendix II A, after drying at a pressure not exceeding 0.7 kPa, is concordant with the reference spectrum of erythromycin (RS 123).
B. Dissolve a quantity of the powdered tablets containing 3 mg of Erythromycin as completely as possible in 2 mL of acetone and add 2 mL of hydrochloric acid; an orange colour is produced which changes to red and then to deep purplish red. Add 2 mL of chloroform and shake; the chloroform layer becomes purple.

Tests

Disintegration

Tablets covered with a gastro-resistant coating comply with the requirements stated under Tablets but operating the apparatus for 1 hour in 0.1m hydrochloric acid.

Related substances

Carry out the method for liquid chromatography, Appendix III D, using solutions (1), (2), (3), (4) and (6) described under Assay.

The chromatographic conditions described under Assay may be used.

Inject 0.1 mL of each solution. For solution (1) allow the chromatography to proceed for 5 times the retention time of the peak corresponding to erythromycin A.

When the chromatograms are recorded using the prescribed conditions the retention time of erythromycin A is about 15 minutes. The retention times relative to erythromycin A are: impurity A, about 0.3; impurity B, about 0.45; erythromycin C, about 0.5; impurity C, about 0.9; impurity D, about 1.4; impurity F, about 1.5; erythromycin B, about 1.8; impurity E, about 4.3.

Identify any peaks in the chromatogram obtained with solution (1) corresponding to impurities E and F using solution (6) and multiply the areas of these peaks by the corresponding correction factors: impurity E, 0.09; impurity F, 0.15. In the chromatogram obtained with solution (1) the area of any peak other than those peaks corresponding to erythromycin A, erythromycin B and erythromycin C, identified from the peaks in the chromatograms obtained with solutions (2) and (3), is not greater than the area of the principal peak in the chromatogram obtained with solution (4) (3%) and the sum of the areas of any such peaks is not greater than 2.3 times the area of the principal peak in the chromatogram obtained with solution (4) (7%). Disregard any peak with an area less than 0.02 times the area of the principal peak in the chromatogram obtained with solution (4) (0.06%).

The content of each of erythromycin B and erythromycin C, as determined under Assay, is not more than 5%.

Assay

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Weigh and powder 20 tablets (if necessary, remove the coating from 20 tablets using a sharp blade, taking care not to damage the cores, weigh the cores and powder). For solution (1) dissolve a quantity of the powdered tablets containing 40 mg of Erythromycin in 10 mL of a mixture of 1 volume of methanol and 3 volumes of citro-phosphate buffer pH 7.0, filter and use the filtrate. Solution (2) contains 0.4% w/v of erythromycin A BPCRS in a mixture of 1 volume of methanol and 3 volumes of citro-phosphate buffer pH 7.0 (solvent A). Solution (3) contains 0.02% w/v of each of erythromycin B BPCRS and erythromycin C BPCRS in solvent A. Solution (4) contains 0.012% w/v of erythromycin A BPCRS in solvent A. For solution (5) dissolve 5 mg of N-demethylerythromycin A BPCRS in solution (3), add 1 mL of solution (2) and sufficient of solution (3) to produce 25 mL. For solution (6) transfer 40 mg of erythromycin A BPCRS to a glass vial and spread evenly such that it forms a layer not more than about 1 mm thick. Heat at 130° for 4 hours, allow to cool and dissolve in sufficient of solvent A to produce 10 mL (generation of impurities E and F). The solutions can be used within one day if stored at 5°.

The chromatographic procedure may be carried out using (a) a column (25 cm × 4.6 mm) packed with styrene-divinylbenzene copolymer (8 µm) with a pore size of 100 nm (PLRP-S is suitable), (b) as mobile phase at a flow rate of 2.0 mL per minute a solution prepared in the following manner: to 50 mL of a 3.5% w/v solution of dipotassium hydrogen orthophosphate adjusted to pH 9.0 with 1m orthophosphoric acid add 400 mL of water, 165 mL of 2-methylpropan-2-ol and 30 mL of acetonitrile and dilute to 1000 mL with water and (c) a detection wavelength of 215 nm. Maintain the temperature of the column at 70° using a water bath for the column and at least one third of the tubing preceding the column.

Inject 0.1 mL of solution (5). Adjust the sensitivity of the detector so that the height of the peaks is at least 25% of the full scale of the recorder. The substances are eluted in the following order: N-demethylerythromycin A, erythromycin C, erythromycin A and erythromycin B. The test is not valid unless the resolution factor between the peaks corresponding to N-demethylerythromycin A and erythromycin C is at least 0.8 and the resolution factor between the peaks corresponding to N-demethylerythromycin A and erythromycin A is at least 5.5. If necessary, adjust the concentration of 2-methylpropan-2-ol in the mobile phase (180 mL has been found to be suitable) or reduce the flow rate to 1.5 or 1.0 mL per minute.

Inject alternately 0.1 mL of solutions (1), (2) and (3). Calculate the content of erythromycin A using the chromatograms obtained with solutions (1) and (2) and from the declared content of C37H67NO13 in erythromycin A BPCRS. Calculate the contents of erythromycin B and erythromycin C using the chromatograms obtained with solutions (1) and (3) and from the declared contents of C37H67NO12 and C36H65NO13 in erythromycin B BPCRS and erythromycin C BPCRS respectively.

Storage

Gastro-resistant Erythromycin Tablets should be protected from light.

Impurities

The impurities limited by the requirements of this monograph include those listed under Erythromycin.