Famciclovir 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

Famciclovir Tablets contain Famciclovir (USP 1-Aug-2022) equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of famciclovir (C₁₄H₁₉N₅O₄).

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

Sample: Transfer a portion of finely powdered Tablets, equivalent to 1000 mg of famciclovir, to a 250-mL volumetric flask, and add 100 mL of acetonitrile. Sonicate for 5 min and centrifuge for 10 min. Pass a portion through a filter of 0.45-μm or finer pore size into a 250-mL evaporating flask. Evaporate the solution to dryness at low heat (about 70°).

Acceptance criteria: Meet the requirements

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

3 ASSAY

3.1 Procedure

Buffer A: 13.8 g/L of monobasic sodium phosphate in water. Adjust with 1 M sodium hydroxide or phosphoric acid to a pH of 4.5 ± 0.05.

Buffer B: 13.8 g/L of monobasic sodium phosphate in water. Adjust with 1 M sodium hydroxide to a pH of 7.0 ± 0.05.

Mobile phase: Methanol and Buffer B (30:70)

Standard solution: 0.1 mg/mL of USP Famciclovir RS in Buffer A

Sample stock solution: Nominally 1 mg/mL of famciclovir prepared as follows. Transfer an amount equivalent to 500 mg of famciclovir, from finely powdered Tablets (NLT 20), to an appropriate volumetric flask. Add about 50% of the flask volume of Buffer A and sonicate for about 15 min with intermittent shaking. Dilute with Buffer A to volume.

Sample solution: Nominally 0.1 mg/mL of famciclovir from Sample stock solution in Buffer A. Pass through a suitable filter of 0.45-μm or finer pore size.

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 222 nm

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

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 20 μL

Run time: NLT 2 times the retention time of famciclovir

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of famciclovir (C₁₄H₁₉N₅O₄) in the portion of Tablets taken:

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

r_U = peak response of famciclovir from the Sample solution

r_S = peak response of famciclovir from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

4.1 Test 1

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Buffer: 6.8 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 3.0. Pass through a suitable filter of 0.45-μm pore size.

Mobile phase: Methanol and Buffer (30:70)

Standard stock solution: 0.55 mg/mL of USP Famciclovir RS prepared as follows. Transfer 55 mg of USP Famciclovir RS to a 100-mL volumetric flask, dissolve in about 50 mL of Medium, and dilute with Buffer to volume.

Standard solution: 0.055 mg/mL of USP Famciclovir RS in Buffer from Standard stock solution

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size, and dilute with Buffer to obtain a concentration similar to that of the Standard solution.

4.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 310 nm

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

Column temperature: 35°

Flow rate: 1 mL/min

Injection volume: 10 μL

4.1.2 System suitability

Sample: Standard solution

4.1.3 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

4.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of famciclovir (C₁₄H₁₉N₅O₄) dissolved:

Result = (r_U /r_S ) × C_S × V × D × (1/L) × 100

r_U = peak response of famciclovir from the Sample solution

r_S = peak response of famciclovir from the Standard solution

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

V = volume of Medium, 900 mL

D = dilution factor of the Sample solution, if applicable

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of famciclovir (C₁₄H₁₉N₅O₄) is dissolved.

4.2 Test 2

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

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Standard solution: 0.55 mg/mL of USP Famciclovir RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter and dilute with Medium, if necessary. Instrumental conditions

Mode: UV

Analytical wavelength: 262 nm

Cell: 5 mm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of famciclovir (C₁₄H₁₉N₅O₄) dissolved:

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

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

V = volume of Medium, 900 mL

D = dilution factor of the Sample solution, if applicable

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of famciclovir (C₁₄H₁₉N₅O₄) is dissolved.

4.3 Test 3

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

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 45 min

Standard solution: 0.55 mg/mL of USP Famciclovir RS prepared as follows. Transfer a suitable amount of USP Famciclovir RS to a suitable volumetric flask, add methanol to about 5% of the flask volume, and dilute with Medium to volume.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size, and dilute with Medium, if necessary, to obtain a concentration similar to that of the Standard solution. Instrumental conditions

Mode: UV

Analytical wavelength: 314 nm

Cell: 0.1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of famciclovir (C₁₄H₁₉N₅O₄) dissolved:

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

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

V = volume of Medium, 900 mL

D = dilution factor of the Sample solution, if applicable

L = label claim (mg/Tablet)

Tolerances: NLT 85% (Q) of the labeled amount of famciclovir (C₁₄H₁₉N₅O₄) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Change to read:

5.1 Organic Impurities

5.2 Solution A: 2.72 g/L of monobasic potassium phosphate in water. Adjust with 1 M phosphoric acid to a pH of 4.0 ± 0.05.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Peak identification solution: 0.004 mg/mL of USP Famciclovir Related Compound A RS and 10 μg/mL of USP Famciclovir Related Compound B RS in Solution A

System suitability solution: 0.5 mg/mL of USP Famciclovir System Suitability Mixture RS in Solution A

Standard solution: 0.001 mg/mL of USP Famciclovir RS in Solution A

Sample solution: Nominally 1 mg/mL of famciclovir in Solution A prepared as follows. Transfer an amount equivalent to 250 mg of famciclovir, from finely powdered Tablets (NLT 10), to a 250-mL volumetric flask. Add about 125 mL of Solution A, and sonicate for 30 min with intermittent shaking. Dilute with Solution A to volume.

5.3 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 25-cm; 5-μm packing L7

5.4 Temperatures

Autosampler: 6°

Column: 50°

Flow rate: 1 mL/min

Injection volume: 20 μL

5.5 System suitability

Samples: System suitability solution and Standard solution

5.6 Suitability requirements

Resolution: NLT 1.2 between propionyl famciclovir and 6-chloro famciclovir, System suitability solution

Relative standard deviation: NMT 5.0% for famciclovir, Standard solution

5.7 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual impurity in the portion of Tablets taken:

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

r_{​​​​​​​U} = peak response of each individual impurity from the Sample solution

r_S = peak response of famciclovir from the Standard solution

C_{​​​​​​​S} = concentration of USP Famciclovir RS in the Standard solution (mg/mL)

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

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

^a 2-Amino-9-[4-hydroxy-3-(hydroxymethyl)butyl]-1H-purin-6(9H)-one; 9-[4-Hydroxy-3-(hydroxymethyl)butyl]guanine.

^b This is a process impurity controlled in the drug substance and is included in the table for peak identification only. This impurity is excluded from the total impurities calculation.

^c 2-[2-(2-Amino-7H-purin-7-yl)ethyl]propane-1,3-diyl diacetate.

^d 2-[2-(2-Acetamido-9H-purin-9-yl)ethyl]propane-1,3-diyl diacetate.

^e 4-(2-Amino-9H-purin-9-yl)-2-(chloromethyl)butyl acetate.

^f 2-[2-(2-Amino-6-chloro-9H-purin-9-yl)ethyl]propane-1,3-diyl diacetate.

^g 2-(Acetoxymethyl)-4-(2-amino-9H-purin-9-yl)butyl propionate.

^h 2-(2-{[9-(4-Acetoxy-3-(acetoxymethyl)butyl]-2-amino-9H-purin-6-yl) amino}ethyl) propane -1,3-diyl diacetate.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Famciclovir RS

USP Famciclovir Related Compound A RS

[2-[2-(2-Amino-9H-purin-9-yl)ethyl]propane-1,3-diol] hydrochloride.

C₁₀H₁₅N₅O₂ · HCl 273.72

USP Famciclovir Related Compound B RS

4-(2-Amino-9H-purin-9-yl)-2-(hydroxymethyl)butyl acetate.

C₁₂H₁₇N₅O₃ 279.30

USP Famciclovir System Suitability Mixture RS

Mixture of famciclovir, propionyl famciclovir, and 6-chloro famciclovir. (Other impurities may also be present.)