Famotidine Tablets
» Famotidine Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of famotidine (C8H15N7O2S3).
Packaging and storage— Preserve in well-closed, light-resistant containers. Store at controlled room temperature.
USP Reference standards 11
USP Famotidine RS Click to View Structure
Identification—
A: Thin-Layer Chromatographic Identification Test 201
Developing solvent— Prepare a mixture of ethyl acetate, methanol, toluene, and ammonium hydroxide (40:25:20:2).
Standard solution— Dissolve USP Famotidine RS in glacial acetic acid to obtain a solution having a concentration of 4 mg per mL.
Test 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.
Procedure— Apply separately 10 µL each of the Standard solution and the Test solution to a suitable thin-layer chromatographic plate coated with a 0.25-mm layer of chromatographic silica gel mixture, allow the spots to dry, and develop the plate in a paper-lined chromatographic chamber equilibrated with Developing solvent for about 1 hour prior to 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: the principal spot from the Test solution corresponds in appearance and RF value to that of the Standard solution.
B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Dissolution 711
Medium: pH 4.5, 0.1 M phosphate buffer; prepared by dissolving 13.6 g of monobasic potassium phosphate in 1 L of water; 900 mL.
Apparatus 2: 50 rpm.
Time: 30 minutes.
Determine the amount of C8H15N7O2S3 dissolved employing one of the following methods.
spectrophotometric method— Determine the amount of C8H15N7O2S3 dissolved from UV absorption at the wavelength of maximum absorbance at about 265 nm, using filtered portions of the solution under test, suitably diluted with Medium if necessary, in comparison with a Standard solution having a known concentration of USP Famotidine RS in the same Medium.
chromatographic method—
Buffer solution and Mobile phase— Proceed as directed in the Assay.
Standard solution— Dissolve an accurately weighed quantity of USP Famotidine RS in Medium to obtain a solution having a known concentration of about 0.14 mg per mL. Dilute this solution with Medium to obtain a solution containing L/900 mg per mL, L being the Tablet label claim, in mg.
Test solution— Use filtered portions of the solution under test.
Chromatographic system— Proceed as directed in the Assay. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the capacity factor, k ¢, is greater than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 50 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the amount of C8H15N7O2S3 dissolved by the formula:
Click to View Image
in which rU and rS are the peak responses for the Test solution and the Standard solution, respectively; CS is the concentration, in mg per mL, of the Standard solution; 900 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; and LC is the Tablet label claim, in mg.
Tolerances— Not less than 75% (Q) of the labeled amount of C8H15N7O2S3 is dissolved in 30 minutes.
for tablets labeled as chewable— Proceed as directed for either of the methods specified above, except for the following:
Time: 45 minutes.
Tolerances— Not less than 80% (Q) of the labeled amount of C8H15N7O2S3 is dissolved in 45 minutes.
for tablets labeled as film-coated— Proceed as directed for either of the methods specified above, except for the following:
Time: 30 minutes.
Tolerances— Not less than 80% (Q) of the labeled amount of C8H15N7O2S3 is dissolved in 30 minutes.
Related compounds—
Buffer solution, Mobile phase, Diluent, System suitability solution, and Chromatographic system— Proceed as directed in the Assay.
Standard solution— Use the Standard preparation as prepared in the Assay.
Test solution— Use the Assay preparation as prepared in the Assay.
Procedure— Separately inject equal volumes (about 50 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of each impurity in the portion of Tablets taken by the formula:
100(1/F)C(D/LN)(ri / rS)
in which F is the relative response factor for each impurity peak (see Table 1 for values); C is the concentration, in mg per mL, of USP Famotidine RS in the Standard solution; L is the labeled amount, in mg, of famotidine in each Tablet; N is the number of Tablets taken to prepare the Test solution; D is the dilution factor used to prepare the Test solution; ri is the peak area obtained for each individual impurity in the Test solution; and rS is the peak area for famotidine in the Standard solution.
Table 1
Approximate Relative
Retention Time
Relative Response
Factor (F)
Name Limit
(%)
0.4 1.0 Impurity A1 1.0
0.7 1.0 Impurity B2 0.5
0.8 1.0 Impurity C3 0.5
1.2 1.3 Impurity D4 0.5
1  3-[2-(diaminomethyleneamino)-1,3-thiazol-4-ylmethylsulfinyl]-N-sulfamoyl-propanamidine
2  3-[2-(diaminomethyleneamino)-1,3-thiazol-4-ylmethylthio]-propanoic acid
3  3-[2-(diaminomethyleneamino)-1,3-thiazol-4-ylmethylthio]-N-sulfamoyl-propanamide
4  3-[2-(diaminomethyleneamino)-1,3-thiazol-4-ylmethylthio]-propanamide
In addition to not exceeding the limits for each impurity in Table 1, not more than 1.5% of total impurities is found.
Uniformity of dosage units 905: meet the requirements.
Assay—
Buffer solution— 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— Prepare a mixture of Buffer solution and acetonitrile (93:7), mix, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
Diluent— Dissolve 6.8 g of monobasic potassium phosphate 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 minutes, and cool to room temperature. Add 2 mL of 0.1 N sodium hydroxide, heat at 80 for 30 minutes, 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 approximately 1 to 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 preparation— Transfer about 10 mg of USP Famotidine RS, accurately weighed, into a 100-mL volumetric flask, add 20 mL of methanol, and sonicate for 5 minutes. Dilute with Diluent to volume, and mix.
Assay preparation— Transfer not fewer than 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 hour. 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 of famotidine per mL.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 275-nm detector and a 4.6-mm × 15-cm column that contains packing L1. The column temperature is maintained at 40. The flow rate is about 1.4 mL per minute. Chromatograph the System suitability solution, and identify the famotidine peak and the peaks due to impurities listed in Table 1. Record the peak responses as directed for Procedure: the resolution, R, between the impurity C and famotidine peaks is not less than 1.3; the resolution, R, between the famotidine and impurity D peaks is not less than 1.3; and the capacity factor, k¢, for the famotidine peak is not less than 2.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is less than 2.0%.
Procedure— Separately inject equal volumes (about 50 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 famotidine (C8H15N7O2S3) in each Tablet taken by the formula:
C(D/N)(rU / rS)
in which C is the concentration, in mg per mL, of USP Famotidine RS in the Standard preparation; D is the dilution factor used to prepare the Assay preparation; N is the number of Tablets taken to prepare the Assay preparation; and rU and rS are the peak areas obtained from the Assay preparation and the Standard preparation, respectively.
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(GCDF2010) General Chapters - Dosage Forms
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