Famotidine for Oral Suspension

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

Famotidine for Oral Suspension contains the equivalent of NLT 90.0% and NMT 110.0% of the labeled amount of famotidine (C₈H₁₅N₇O₂S₃) when constituted as directed. It contains one or more suitable buffers, colors, diluents, avors, and preservatives.

2 IDENTIFICATION

A. The retention time of the famotidine peak from the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

Buffer A: Dissolve 13.6 g of sodium acetate trihydrate in 900 mL of water, and adjust with glacial acetic acid to a pH of 6.0 ± 0.1, before final dilution to 1 L.

Buffer B: Dissolve 13.6 g of monobasic sodium phosphate in 900 mL of water, adjust with 1 M sodium hydroxide to a pH of 7.0 ± 0.1, and dilute with water to 1 L.

Solution A: Acetonitrile and Buffer A (7:93)

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and Buffer B (7:93)

Standard solution: 0.16 mg/mL of USP Famotidine RS in Diluent

Sample solution: Transfer to a 100-mL volumetric flask a portion of Famotidine for Oral Suspension, equivalent to about 40 mg of famotidine, freshly mixed and free from air bubbles and constituted as directed in the labeling. Add 10 mL of methanol, sonicate for 5 min, add 70 mL of Diluent, sonicate for an additional 5 min, and dilute with Diluent to volume. Dilute 10.0 mL of this solution with Diluent to 25.0 mL, and filter.

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 268 nm

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

Column temperature: 35°

Flow rate: 1.5 mL/min

Injection size: 20 μL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Column efficiency: Greater than 2000 theoretical plates

Tailing factor: NMT 2

Relative standard deviation: NMT 2.0%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of famotidine (C₈H₁₅N₇O₂S₃) in the portion of Famotidine for Oral Suspension taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_{​​​​​​​U} = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Famotidine RS in the Standard solution (mg/mL)

C_{​​​​​​​U} = nominal concentration of famotidine in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉: Meets the requirements for Content Uniformity. For the product in multi-dose containers, the unit is a 5-mL aliquot of the suspension, constituted as directed in the labeling.

5 IMPURITIES

5.1 Organic Impurities

Mobile phase, Diluent, Standard solution, Sample solution and Chromatographic system: Proceed as directed in the Assay.

System suitability stock solution: Transfer 16 mg of famotidine to a 50-mL volumetric flask. Dissolve in 1.0 mL of 1 N hydrochloric acid, heat at 80° for 30 min, and cool to room temperature. Add 2.0 mL of 1 N sodium hydroxide, heat at 80° for 30 min, and cool to room temperature.

Add 1.0 mL of 1 N hydrochloric acid to neutralize, and dilute with Diluent to volume.

System suitability solution: Transfer 16 mg of famotidine to a 50-mL volumetric flask. Add 10 mL of Diluent, and sonicate to dissolve. Add 5 drops of Hydrogen peroxide solution, heat at 80° for 15 min, and cool to room temperature. Add 20 mL of System suitability stock solution, and dilute with Diluent to volume.

5.2 System suitability

Samples: Standard solution and System suitability solution

[Note-Identify the components of the System suitability solution based on the relative retention times listed in Table 2.]

5.3 Suitability requirements

Resolution: Greater than 1.5 between famotidine and famotidine propanamide, System suitability solution

Column efficiency: Greater than 2000 theoretical plates, Standard solution

Tailing factor: NMT 2, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

5.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the total of famotidine sulfamoyl propanamide and famotidine propanamide in the portion of Famotidine for

Oral Suspension taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = sum of the peak areas for famotidine sulfamoyl propanamide and famotidine propanamide from the Sample solution

r_S = peak area of famotidine from the Standard solution

C_S = concentration of USP Famotidine RS in the Standard solution (mg/mL)

C_U = nominal concentration of famotidine in the Sample solution (mg/mL)

5.5 Acceptance criteria

Total of famotidine sulfamoyl propanamide and famotidine propanamide: Less than 2.0%

Table 2

^a 3-[[2-(Diaminomethyleneamino)thiazol-4-yl]methylsulfinyl]-N′-sulfamoylpropanimidamide.

^b 3-[[2-(Diaminomethyleneamino)thiazol-4-yl]methylthio]propanoic acid.

^c 3-[[2-(Diaminomethyleneamino)thiazol-4-yl]methylthio]-N-sulfamoylpropanamide.

^d 3-[[2-(Diaminomethyleneamino)thiazol-4-yl]methylthio]propanamide.

6 SPECIFIC TESTS

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: The total aerobic microbial count is NMT 102cfu/g. The total combined molds and yeasts count is NMT 102 cfu/g. It meets the requirements of the tests for the absence of Salmonella species and Escherichia coli.

pH 〈791〉: 6.5–7.5, in the suspension constituted as directed in the labeling

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, protected from light. Store at 25°, excursions permitted between 15° and 30°.

USP Reference Standards 〈11〉

USP Famotidine RS