Famotidine 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

Famotidine Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of famotidine (C₈H₁₅N₇O₂S₃).

2 IDENTIFICATION

A. THIN-LAYER CHROMATOGRAPHIC IDENTIFICATION TEST (201)

Standard solution: 4 mg/mL of USP Famotidine RS in glacial acetic acid

Sample solution: Transfer a portion of finely powdered Tablets, equivalent to about 40 mg of famotidine, to a 10-mL volumetric flask. Dissolve in glacial acetic acid with the aid of sonication, dilute with glacial acetic acid to volume, and centrifuge to get a clear liquid.

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Application volume: 10 µL

Developing solvent system: Ethyl acetate, methanol, toluene, and ammonium hydroxide (40:25:20:2)

Analysis: Allow the spots to dry, and develop the plate in a paper-lined chromatographic chamber equilibrated with Developing solvent system for about 1 h before use. Allow the chromatogram to develop until the solvent front has moved about 15 cm. Remove the plate, air-dry, and examine the plate under short-wavelength UV light.

Acceptance criteria: The principal spot from the Sample solution corresponds in appearance and R_F value to that of the Standard solution.

B. The retention time of the major peak in the Sample solution corresponds to that in the Standard solution, as obtained in the Assay.

3 ASSAY

PROCEDURE

Buffer: Dissolve 13.6 g of sodium acetate trihydrate in 750 mL of water. Add 1 mL of triethylamine, adjust with glacial acetic acid to a pH of 6.0, and dilute with water to 1 L.

Mobile phase: Acetonitrile and Buffer (7:93)

Diluent: Dissolve 6.8 g of potassium phosphate, monobasic in 750 mL of water, adjust with 1 M potassium hydroxide to a pH of 6.0, and dilute with water to 1 L.

System suitability stock solution: Transfer 10 mg of famotidine to a 50-mL volumetric flask. Add 1 mL of 0.1 N hydrochloric acid, heat at 80° for 30 min, and cool to room temperature. Add 2 mL of 0.1 N sodium hydroxide, heat at 80° for 30 min, cool to room temperature, and neutralize by adding 1 mL of 0.1 N hydrochloric acid. Dilute with Diluent to volume. Transfer 10 mL of this solution to a separate 50-mL volumetric flask containing 5 mg of famotidine dissolved in 8 mL of methanol. Dilute with Diluent to volume. Transfer 25 mL of this solution to a 50-mL volumetric flask, and dilute with Diluent to volume. [NOTE-This solution is stable for up to 1 month.]

System suitability solution: Transfer 1-1.5 mL of the System suitability stock solution to a suitable container, add 1 drop of Hydrogen peroxide solution, and mix well.

[NOTE-Prepare fresh daily.]

Standard solution: Transfer 10 mg of USP Famotidine RS to a 100-mL volumetric flask, add 20 mL of methanol, and sonicate for 5 min. Dilute with Diluent to volume.

Sample solution: Transfer NLT 10 Tablets to a 1-L volumetric flask. Add 200 mL of Diluent, and swirl to erode the Tablets. Add 200 mL of methanol, and stir by mechanical means at 300 rpm for 1 h. Dilute with Diluent to volume, mix, and filter. Quantitatively dilute a portion of the clear filtrate with Diluent to obtain a solution containing about 0.1 mg/mL of famotidine.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 275 nm

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

Column temperature: 40°

Flow rate: 1.4 mL/min

Injection size: 50 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

[NOTE-Identify peaks using Table 1.]

Resolution: NLT 1.3 between the famotidine sulfamoyl propanamide and famotidine peaks, and NLT 1.3 between the famotidine and famotidine propanamide peaks, System suitability solution

Capacity factor: NLT 2.0 for the famotidine peak, System suitability solution

Relative standard deviation: Less than 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of famotidine (C₈H₁₅N₇O₂S₃) in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) x 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

Change to read:

4.1 DISSOLUTION (711)

4.1.1 Test 1 (RB 1-Aug-2023)

Medium: pH 4.5, 0.1 M phosphate buffer (13.6 g/L of potassium phosphate, monobasic); 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Determine the amount of C₈H₁₅N₇O₂S₃ dissolved using one of the following methods.

Spectrophotometric method

Standard solution: USP Famotidine RS in Medium in a concentration similar to the one expected in the Sample solution

Sample solution: Pass a portion of the sample under test through a suitable filter.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 265 nm

Chromatographic method

Buffer, Mobile phase, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.14 mg/mL of USP Famotidine RS in Medium. Dilute this solution with Medium to obtain a solution containing (L/900) mg/mL, where L is the Famotidine Tablet label claim, in mg.

Sample solution: Pass a portion of the solution under test through a suitable filter.

System suitability

Sample: Standard solution

Suitability requirements

Capacity factor: Greater than 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the amount of famotidine (C₈H₁₅N₇O₂S₃) dissolved:

Result = (r_U/r_S) x (C_S/L) x V x 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)

L = label claim, mg/Tablet

V = volume of Medium, 900 mL

Tolerances: NLT 75% (Q) of the labeled amount of famotidine (C₈H₁₅N₇O₂S₃) is dissolved.

For Tablets labeled as chewable

Proceed as directed for either of the methods specified above, except for the following:

Time: 45 min

Tolerances: NLT 80% (Q) of the labeled amount of famotidine (C₈H₁₅N₇O₂S₃) is dissolved.

For Tablets labeled as film-coated

Proceed as directed for either of the methods specified above, except for the following:

Time: 30 min

Tolerances: NLT 80% (Q) of the labeled amount of famotidine (C₈H₁₅N₇O₂S₃) is dissolved.

4.1.2 Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2

Medium: pH 4.5 phosphate buffer (Dissolve 13.6 g of potassium phosphate, monobasic in 1000 mL of water, and adjust with 1 N sodium hydroxide or 1 N hydrochloric acid to a pH of 4.5.); 500 mL

Apparatus 2: 50 rpm

Time: 30 min

Standard solution: 0.02 mg/mL of USP Famotidine RS in Medium. Sonicate to dissolve.

[NOTE-It is recommended to maintain the water bath temperature at 10°-15° during sonication.]

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding first few milliliters of filtrate. Dilute with Medium, if necessary, to obtain a concentration similar to that of the Standard solution.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 265 nm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount famotidine (C₈H₁₅N₇O₂S₃) dissolved:

Result = (A_U/A_S) x C_S x V x D x (1/L) × 100

A_U = UV absorbance from the Sample solution

A_S = UV absorbance from the Standard solution

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

V = volume of Medium, 500 mL

D = dilution factor for the Sample solution

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of famotidine (C₈H₁₅N₇O₂S₃) is dissolved. (RB 1-Aug-2023)

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

ORGANIC IMPURITIES

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) x (1/F) × 100

r_U = peak area of each impurity 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)

F = relative response factor for each impurity (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^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 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in well-closed, light-resistant containers. Store at controlled room temperature.

Add the following:

6.2 LABELING

When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used. (RB 1-Aug-2023)

6.3 USP REFERENCE STANDARDS (11)

USP Famotidine RS