Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl for Oral Suspension
» Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl for Oral Suspension is a dry mixture of Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl with one or more suitable buffers, colors, flavors, surfactants, and suspending agents. It contains the equivalent of not less than 90.0 percent and not more than 120.0 percent of the labeled amount of erythromycin (C37H67NO13) and the equivalent of not less than 90.0 percent and not more than 115.0 percent of the labeled amount of sulfisoxazole (C11H13N3O3S).
[noteWhere Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl for Oral Suspension is prescribed, without reference to the quantity of erythromycin or sulfisoxazole contained therein, a product containing 40 mg of erythromycin and 120 mg of sulfisoxazole per mL when constituted as directed in the labeling shall be dispensed. ]
Packaging and storage Preserve in tight containers.
USP Reference standards 11
Identification To a quantity of the Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl for Oral Suspension add a volume of methanol sufficient to yield a solution having a concentration equivalent to about 2.5 mg of erythromycin per mL. Shake this mixture by mechanical means for about 30 minutes. Centrifuge a portion of this mixture, and use the clear supernatant as the test solution. Prepare a solution of USP Erythromycin Ethylsuccinate RS in methanol containing about 3 mg per mL (Standard solution A). Prepare a solution of USP Sulfisoxazole Acetyl RS in methanol containing about 8.7 mg per mL (Standard solution B). Apply separately 10 µL each of the test solution and the two Standard solutions to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture, and allow to dry. Place the plate in an unlined chromatographic chamber, and develop the chromatograms in a solvent system consisting of a mixture of methanol and chloroform (85:15) until the solvent front has moved about 9 cm. Remove the plate from the chamber, mark the solvent front, and allow the solvent to evaporate. Spray the plate with a mixture of dehydrated alcohol, p-methoxybenzaldehyde, and sulfuric acid (90:5:5). Heat the plate at 100 for 10 minutes, and examine the chromatograms, in which the erythromycin and succinic acid moieties appear as black-to-purple spots and the sulfisoxazole acetyl appears as a yellow spot: the RF values of the principal black-to-purple spots obtained from the test solution correspond to those obtained from Standard solution A; and the RF value of the principal yellow spot obtained from the test solution corresponds to that obtained from Standard solution B.
Uniformity of dosage units 905
for solid packaged in single-unit containers: meets the requirements for Content Uniformity with respect to erythromycin and sulfisoxazole.
Deliverable volume 698: meets the requirements.
pH 791: between 5.0 and 7.2, in the suspension constituted as directed in the labeling.
Loss on drying 731: Dry about 100 mg in a capillary-stoppered bottle in vacuum at 60 for 3 hours: it loses not more than 1.0% of its weight.
Assay for erythromycin Constitute Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl for Oral Suspension as directed in the labeling, and allow to stand for 1 hour. Gently shake the suspension, transfer 5.0 mL to a high-speed blender jar containing 195.0 mL of methanol, and blend for 4 ± 1 minutes. Proceed as directed under AntibioticsMicrobial Assays 81, using an accurately measured volume of this stock test solution diluted quantitatively and stepwise with Buffer No. 3 to yield a Test Dilution having a concentration assumed to be equal to the median dose level of the Standard (1.0 µg of erythromycin per mL).
Assay for sulfisoxazole
Mobile solvent Mix 40 volumes of acetonitrile and 60 volumes of water. The acetonitrile concentration may be varied to meet system suitability requirements and to provide a suitable elution time for sulfisoxazole acetyl. Pass the solution through a membrane filter having a 1-µm or finer porosity.
Internal standard solution Prepare a solution of benzanilide in acetonitrile having a concentration of about 0.33 mg per mL. Pass the solution through a membrane filter having a 1-µm or finer porosity.
Standard preparation Prepare a solution of USP Sulfisoxazole Acetyl RS in Internal standard solution having a known concentration of about 1 mg per mL.
Assay preparation Constitute Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl for Oral Suspension as directed in the labeling, and allow to stand for 1 hour. Gently shake the suspension, transfer to a 125-mL separator an accurately measured volume of it, equivalent to about 600 mg of sulfisoxazole, and extract with three 75-mL portions of chloroform. Collect the chloroform extracts in a 250-mL volumetric flask, dilute with chloroform to volume, and mix. Pass a portion of this solution through a membrane filter having a 1-µm or finer porosity. Pipet 4 mL of the filtrate into a glass-stoppered, 25-mL conical flask, and evaporate with the aid of a current of dry air to dryness. Add 10.0 mL of Internal standard solution, and mix.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 254-nm detector and a 4-mm × 30-cm column that contains packing L1. The flow rate is about 1.2 mL per minute. Chromatograph replicate injections of the Standard preparation, and record the peak responses as directed for Procedure: the resolution factor between sulfisoxazole acetyl and benzanilide is not less than 3.0.
Procedure Separately inject equal volumes (about 5 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of sulfisoxazole (C11H13N3O3S) in each mL of the constituted suspension taken by the formula:
(267.31/309.35)(625C/V)(RU / RS)in which 267.31 and 309.35 are the molecular weights of sulfisoxazole and sulfisoxazole acetyl, respectively; C is the concentration, in mg, of USP Sulfisoxazole Acetyl RS in each mL of the Standard preparation; V is the volume, in mL of constituted suspension taken; and RU and RS are the ratios of peak responses of sulfisoxazole acetyl peak to benzanilide peak obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 3090Pharmacopeial Forum: Volume No. 29(3) Page 626