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Category Antibacterial.

      Erythromycin Stearate Tablets contain the equivalent of not less than 90.0 per cent and not more than 120.0 per cent of the labelled amount of C₃₇H₆₇NO₁₃.

Strengths available 250 and 500 mg (base).

Dose Adults: 250 mg every 6 hours or 500 mg every 12 hours. The maximum total dose should not exceed 4 g per day.

      Children: 7.5 to 12.5 mg per kg of body weight every 6 hours or 15 to 25 mg per kg of body weight every 12 hours.

      Severe infections: 15 to 25 mg per kg of body weight every 6 hours.

Contra-indication; Warning; Precaution See under Erythromycin, p. 99.

Packaging and storage Erythromycin Stearate Tablets shall be kept in tightly closed containers, protected from light.

Labelling

The label on the container states the quantity equivalent to the amount of erythromycin.

Identification

       A. Shake a portion of the powdered tablets equivalent to 100 mg of erythromycin with 10 ml of water. Decant the supernatant liquid and discard. Extract the residue by shaking with 10 ml of methanol, filter the extract and evaporate to dryness. The infrared absorption spectrum of the residue, after drying at a pressure not exceeding 0.7 kPa (about 5 Torr), is concordant with the spectrum obtained from Erythromycin Stearate RS (Appendix 2.1) or with the reference spectrum of Erythromycin Stearate.

      B. Carry out the test as described in the “Thin-layer Chromatography” (Appendix 3.1), using silica gel G as the coating substance and a mixture of 17 volumes of methanol and 3 volumes of chloroform as the mobile phase but developing the chromatogram in an unlined chromatographic chamber. Apply separately to the plate, 20 μl of each of the following solutions. For solution (A), add a volume of methanol to a portion of the powdered tablets, sufficient to yield a solution containing the equivalent of 5 mg of erythromycin per ml. Shake this mixture by mechanical means for 30 minutes. Centrifuge a portion of this mixture, and use the clear supernatant liquid. Solution (B) contains 8 mg/ml of Erythromycin Stearate RS in methanol. After removal of the plate, allow it to dry in air, spray with a 0.2 per cent w/v solution of 2,7-dichlorofluorescein in methanol, and examine the plate under ultraviolet light (366 nm). The principal fluorescent spots in the chromatogram obtained from solution (A) correspond to those obtained from solution (B). Then spray the plate with a mixture of 18 volumes of absolute ethanol, 1 volume of 4-methoxybenzaldehyde and 1 volume of sulfuric acid. Heat the plate at 100º for 10 minutes. Erythromycin appears as a black-to-purple spot: the principal spot obtained from solution (A) corresponds to that obtained from solution (B).

      C. Dissolve a portion 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.

      D. Extract a portion of the powdered tablets equivalent to 50 mg of erythromycin with 10 ml of chloroform, filter and evaporate to dryness. Heat 100 mg of the residue gently with 5 ml of 2 M hydrochloric acid and 10 ml of water until the solution boil: oily globules rise to the surface. Cool, remove the fatty layer, heat it with 3 ml of 0.1 M sodium hydroxide, and allow to cool: the solution sets to a gel. Add 10 ml of hot water and shake: the solution froths. To 1 ml add a 10 per cent w/v solution of calcium chloride: a granular precipitate is produced which is insoluble in hydrochloric acid.

Loss on drying Not more than 5.0 per cent w/w after drying about 100 mg in a capillary-stoppered bottle at 60º at a pressure not exceeding 2.7 kPa (about 20 Torr) for 3 hours (Appendix 4.15).

Dissolution Carry out the test as described in the “Dissolution Test” (Appendix 4.24).

      Dissolution medium: pH 6.8 phosphate buffer; 900 ml.

      Apparatus 2: 100 rpm.

      Time: 120 minutes.

      Standard solution Dissolve an accurately weighed quantity of Erythromycin Stearate RS in methanol (not more than 1 ml of methanol for each 14 mg of the Reference Substance), and dilute with water, quantitatively and with mixing, to obtain a stock solution containing about 0.56 mg per ml. Immediately prior to use, dilute the stock solution quantitatively with water to obtain a solution having a known concentration of about 280 μg per ml.

      Test solution If necessary, dilute a filtered portion of the test solution with Dissolution medium to obtain a solution having a concentration of about 0.28 mg of erythromycin per ml, and mix.

      Procedure Transfer 5.0-ml portions of Standard solution and Test solution to separate 25-ml volumetric flasks, and treat each as follows. Add 2.0 ml of water, and allow to stand for 5 minutes with intermittent swirling. Add 15.0 ml of 0.25 M sodium hydroxide, dilute with Dissolution medium to volume, and mix. Heat to 60º for 5 minutes, and allow to cool. Concomitantly measure the absorbances of these solutions at the maximum at about 236 nm (Appendix 2.2), using a blank solution similarly prepared, except that 2.0 ml of 0.25 M sulfuric acid is substituted for the 2.0 ml of water. Calculate the amount of C₃₇H₆₇NO₁₃ dissolved.

      Tolerances Not less than 75 per cent (Q) of the labelled amount C₃₇H₆₇NO₁₃ is dissolved in 120 minutes.

      Assay Place not less than four Erythromycin Stearate Tablets in a high-speed glass blend jar with 200 ml of methanol and blend for 3 minutes. Add 300 ml of Buffer 2 and blend for 3 minutes. Proceed as directed under the microbiological assay of erythromycin according to the “Microbiological Assay of Antibiotics” (Appendix 6.10).

      Other requirements Comply with the requirements described under “Tablets” (Appendix 1.16).