Erythromycin Delayed-Release Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Erythromycin Delayed-Release Tablets contain NLT 90.0% and NMT 120.0% of the labeled amount of erythromycin (C₃₇H₆₇NO₁₃).

2 IDENTIFICATION

A. THIN-LAYER CHROMATOGRAPHY

Standard solution: 2.5 mg/mL of USP Erythromycin RS in methanol

Sample solution: Nominally 2.5 mg/mL of erythromycin from powdered Tablets in methanol

Chromatographic system

(See Chromatography (621), General Procedures. Thin-Layer Chromatography.)

Mode: TLC

Adsorbent: 0.25-mm layer of chromatographic silica gel

Application volume: 10 μί

Developing solvent system: Methanol and chloroform (85:15)

Spray reagent: Alcohol, p-methoxybenzaldehyde, and sulfuric acid (90:5:5)

Analysis

Samples: Standard solution and Sample solution

Place the plate in an unlined chromatographic chamber, and develop the chromatogram until the solvent front has moved about 7 cm. Remove the plate from the chamber, mark the solvent front, and allow the solvent to evaporate. Spray the plate with Spray reagent. Heat the plate at 100° for 10 min, and examine the chromatogram, in which erythromycin appears as a black-to-purple spot.

Acceptance criteria: The R, value of the principal spot of the Sample solution corresponds to that of the Standard solution.

3 ASSAY

ANTIBIOTICS-MICROBIAL ASSAYS (81)

Sample solution: Place NLT 4 Tablets in a high-speed glass blender jar with 200 ml of methanol, and blend for 3 min. Add 300 mL of Buffer B.3, and blend for 3 min.

Analysis: Proceed as directed in the chapter. Dilute the Sample solution with Buffer B.3 to obtain a Test Dilution having a concentration that is nominally equivalent to the median level of the standard.

Acceptance criteria: 90.0%-120.0%

4 PERFORMANCE TESTS

Change to read:

DISSOLUTION (711)

Test 1: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 1.

Proceed as directed in Dissolution (711), Procedure. Apparatus 1 and Apparatus 2. Delayed-Release Dosage Forms, Method B Procedure.

Acid stage

Medium: Simulated gastric fluid TS, without pepsin; 900 ml.

Apparatus 1: 100 rpm.

Time: 60 min.

Analysis: Do not analyze the sample at this stage.

Buffer stage

Medium: 0.05 M pH 6.8 phosphate buffer (see Reagents. Indicators, and Solutions-Buffer Solutions); 900 mL _{(ERR 1-Apr-2023)}

Apparatus 1: 100 rpm

Time: 60 min

Buffer: pH 1.2 buffer (see Reagents, Indicators, and Solutions-Buffer Solutions)

Solution A: 1 g/L of bromocresol purple in pH 4.5 phosphate buffer

Standard solution: Dissolve USP Erythromycin RS in Medium to obtain a concentration similar to that of the Sample solution.

Sample solution: If necessary, dilute a filtered portion of the solution under test with Medium to obtain a solution containing about 0.28 mg/mL of erythromycin.

Detector: UV 410 nm

Analysis

Samples: Standard solution and Sample solution

Transfer 2.0 mL of the Standard solution and the Sample solution to individual separators of a suitable size. Add 6 mL of Buffer and 8 mL of Solution A, and mix. Extract with 40.0 mL of chloroform. Determine the amount of erythromycin (C₃₇H₆₇NO₁₃) dissolved from UV absorbances of the chloroform extracts.

Tolerances: NLT 75% (Q) of the labeled amount of erythromycin (C₃₇H₆₇NO₁₃) is dissolved.

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2. Proceed as directed under Test 1, except to use Apparatus 2 at 75 rpm.

Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.

Acid stage

Acid stage medium: Simulated gastric fluid TS, without enzyme, 900 mL

Apparatus 1: 100 rpm

Time: 60 min

Solution A: 3.6 g/L of dibasic sodium phosphate in water. Adjust with diluted phosphoric acid to a pH of 9.0.

Mobile phase: Solution A and acetonitrile (1:1)

Solution B: 6.8 g/L of monobasic potassium phosphate and 1.2 g/L of sodium hydroxide in water

Peak identification solution: 0.05 mg/mL of USP Erythromycin B RS and USP Erythromycin C. RS prepared as follows. Transfer 2.5 mg each of USP Erythromycin B RS and USP Erythromycin C RS to a 50-mL volumetric flask, add 12.5 mL of methanol, sonicate to dissolve, and dilute with Solution B to volume.

[NOTE-The typical retention times of erythromycin C and erythromycin B are 4.2 and 13.4 min, respectively.)

Standard solution: 2.5 mg/mL of USP Erythromycin RS prepared as follows. Transfer 125 mg of USP Erythromycin RS to a 50-mL volumetric flask, add 12.5 mL of methanol, sonicate to dissolve, and dilute with Solution B to volume.

[NOTE-The typical retention time of erythromycin A is 7.8 min.]

Sample solution 1: Determine the average Tablet weight by weighing NLT 20 Tablets. Carefully transfer the appropriate number of intact Tablets into a suitable volumetric flask (5 Tablets into a 500-mL flask for 250-mg Tablets, 8 Tablets into a 1000 mL flask for 333-mg Tablets, and 5 Tablets into a 1000-mL flask for 500-mg Tablets). Add methanol to about 25% of the final volume, and sonicate at room temperature for about 30 min with intermittent shaking. Further add about 25% of the final volume of Solution B and sonicate at room temperature for about 30 min with intermittent shaking. Dilute to volume with Solution B and mix well. Centrifuge at 5000 rpm for 5 min and pass the supernatant through a polyvinylidene fluoride (PVDF) or other suitable filter of 0.45-um pore size. Discard the first 5 mL of the filtrate.

Sample solution 2: At the end of Acid stage dissolution, discard Acid stage medium and carefully transfer 1 Tablet from the dissolution vessel into a suitable volumetric flask (use a 100-mL flask for 250-mg Tablets, 200-mL flask for 333-mg Tablets, and 200-mL flask for 500-mg Tablets). Add methanol to about 25% of the final volume, and sonicate at room temperature for about 30 min with intermittent shaking. Further add about 25% of the final volume of Solution B and sonicate at room temperature for about 30 min with intermittent shaking. Dilute to volume with Solution B and mix well. Centrifuge at 5000 rpm for 5 min and pass the supernatant through a PVDF or other suitable filter of 0.45-um pore size. Discard the first 5 mL of the filtrate..

Blank: Solution B and methanol (75:25)

Chromatographic system

(See Chromatography (621), System Suitability)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm x 25-cm; 5-µm packing L1

Temperature

Autosampler: 4

Column: 50°

Flow rate: 1.5 mL/min

Injection volume: 25 µL

System suitability

Sample: Standard solution

[NOTE-The relative retention times of erythromycin C, erythromycin A, and erythromycin B are 0.53, 1.00, and 1.75, respectively)

Suitability requirements

Tailing factor: NMT 2.0 for erythromycin A peak

Relative standard deviation: NMT 2.0% of the sum of erythromycin A, erythromycin B, and erythromycin C

Analysis

Samples: Standard solution, Sample solution 1, and Sample solution 2

Calculate the erythromycin content (A) as a percentage of the labeled amount of erythromycin:

Result = (r_u /r_s ) × W × P × (1/D_s ) × D₁ × (1/L) × 100

r_u = peak response of sum of erythromycin A, erythromycin B, and erythromycin C from Sample solution 1

r_s = peak response of sum of erythromycin A, erythromycin B, and erythromycin C from the Standard solution

W = standard weight of USP Erythromycin RS to prepare the Standard solution (mg)

P = content of erythromycin A, erythromycin B, and erythromycin C in USP Erythromycin RS (mg/mg)

D_s = dilution factor used in preparing the Standard solution (mL)

D₁ = dilution factor used in preparing Sample solution 1 (mL)

L = label claim (mg/Tablet)

Calculate the percentage (T) of the labeled amount of erythromycin retained:

Result = (r_u /r_s ) × W × P × (1/D_s ) × D₂ × (1/L) × 100

r_u = peak response of sum of erythromycin A, erythromycin B, and erythromycin C from Sample solution 2

r_s = peak response of sum of erythromycin A, erythromycin B, and erythromycin C from the Standard solution

W = standard weight of USP Erythromycin RS to prepare the Standard solution (mg)

P = content of erythromycin A, erythromycin B, and erythromycin C in USP Erythromycin RS (mg/mg)

D_s = dilution factor used in preparing the Standard solution (mL)

L = label claim (mg/Tablet)

D₂ = dilution factor used in preparing Sample solution 2 (mL)

Calculate the percentage of the labeled amount of erythromycin dissolved in Acid stage:

Result = A − T

A = erythromycin content as a percentage of the labeled amount

T = percentage of the labeled amount of erythromycin retained

[Note—If T is greater than A, consider the result to be zero.]

Tolerances: NMT 10% of the labeled amount of erythromycin is dissolved.

Buffer stage

Buffer stage medium: 6.8 g/L. monobasic potassium phosphate in water with pH 6.8 adjusted by 5 N sodium hydroxide: 900 ml

Apparatus 1: 100 rpm

Time: 35 min.

Solution A and Mobile phase: Prepare as directed in Acid stage.

Standard solution: Transfer a suitable amount of USP Erythromycin RS into an appropriate volumetric flask. See Table 1. Add methanol to about 5% of the final volume and sonicate to dissolve. Dilute with Buffer stage medium to volume with intermittent shaking and mix well.

[NOTE-The typical retention time of erythromycin A is 3.8 min.]

Table 1

Sample solution: Prepare as directed in Acid stage with a new set of Tablets. After 60 min with Acid stage medium, immediately replace with Buffer stage medium. After 35 min, pass a portion of the solution through a PVDF or other suitable lter of 0.45-µm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Temperature

Autosampler: 5°

Column: 50°

Flow rate: 2.0 mL/min

Injection volume: 100 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0 for erythromycin A peak

Relative standard deviation: NMT 2.0% of erythromycin A

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of erythromycin dissolved:

Result = (r_u /r_s ) × C_s × (1/L) × V × 100

r_u = peak response of erythromycin A from the Sample solution

r_s = peak response of erythromycin A from the Standard solution

C_s = concentration of erythromycin A in the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of buffer medium

Tolerances: NLT 80% (Q) of the labeled amount of erythromycin is dissolved.

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 SPECIFIC TESTS

WATER DETERMINATION (921), Method

Analysis: Use 20 ml. of methanol containing 10% of imidazole in place of methanol in the titration vessel.

Acceptance criteria: NMT 6.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

LABELING: The labeling indicates the Dissolution Test with which the product complies.

USP REFERENCE STANDARDS (11)

USP Erythromycin RS

USP Erythromycin B RS

USP Erythromyon C RS