Ribavirin Capsules

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

Ribavirin Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of ribavirin (C₈H₁₂N₄O₅).

2 IDENTIFICATION

A.

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

Procedure

Mobile phase: Water. Adjust with sulfuric acid to a pH of 2.5.

Standard solution: 0.025 mg/mL of USP Ribavirin RS in Mobile phase

Sample stock solution:

Transfer an equivalent to 50 mg of ribavirin, from contents of Capsules (NLT 20), to a 100-mL volumetric flask.

Add about 50 mL of Mobile phase, and sonicate with occasional shaking for about 20 min.

Cool to room temperature, and dilute with Mobile phase to volume.

Sample solution:

Nominally 0.025 mg/mL of ribavirin in Mobile phase from Sample stock solution.

Pass the solution through a suitable filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 207 nm

Column: 7.8-mm × 15-cm; 7-µm packing L17

Column temperature: 65°

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements:

Tailing factor: 0.7–1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ribavirin (C₈H₁₂N₄O₅) in the portion of Capsules taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

Cₛ = concentration of USP Ribavirin RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of ribavirin in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Medium: Water; 900 mL

Apparatus 1: 100 rpm

Time: 30 min

Determine the percentage of the labeled amount of ribavirin (C₈H₁₂N₄O₅) dissolved by using one of the following procedures.

Procedure 1

Mobile phase: Proceed as directed in the Assay.

Standard solution: 22.5 µg/mL of USP Ribavirin RS in Medium

Sample solution:

Pass the solution through a suitable filter of 0.45-µm pore size.

Transfer 5.0 mL of the filtrate to a 50.0-mL volumetric flask, and dilute with Medium to volume.

Chromatographic system

Mode: LC

Detector: UV 207 nm

Column: 7.8-mm × 30-cm; 9-µm packing L17

Column temperature: 65°

Flow rate: 1.5 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements:

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ribavirin (C₈H₁₂N₄O₅) dissolved:

Result = (rᵤ / rₛ) × (Cₛ / L) × V × D × 100

rᵤ = peak area from the Sample solution

rₛ = peak area from the Standard solution

Cₛ = concentration of the Standard solution (mg/mL)

L = label claim (mg/Capsule)

V = volume of Medium, 900 mL

D = dilution factor of the solution under test

Procedure 2

Sulfuric acid solution: 3% sulfuric acid

Mobile phase: Water. Adjust with Sulfuric acid solution to a pH of 2.5.

Standard solution: 0.02 mg/mL of USP Ribavirin RS in Medium

Sample solution:

Pass the solution through a suitable filter of 0.8-µm pore size.

Transfer 5.0 mL of the filtrate to a 50-mL volumetric flask, and dilute with water to volume.

Chromatographic system

Mode: LC

Detector: UV 207 nm

Column: 7.8-mm × 10-cm; 9-µm packing L17

Column temperature: 40 ± 2°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements:

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of ribavirin (C₈H₁₂N₄O₅) dissolved:

Result = (rᵤ / rₛ) × (Cₛ / L) × V × D × 100

rᵤ = peak area from the Sample solution

rₛ = peak area from the Standard solution

Cₛ = concentration of the Standard solution (mg/mL)

L = label claim (mg/Capsule)

V = 900 mL

D = dilution factor of the solution under test

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

Test 2

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

Medium: Water; 900 mL, deaerated

Apparatus 1: 100 rpm

Time: 15 min

Buffer:

4 g/L of sodium dihydrogen orthophosphate dihydrate in water.

Adjust with 5% (v/v) sodium hydroxide solution to a pH of 5.0.

Filter through a suitable 0.45-µm or finer filter.

Mobile phase: Acetonitrile and Buffer (2:98)

Standard solution: 0.22 mg/mL of USP Ribavirin RS in Medium (sonicate if needed)

Sample solution: Filter through a 0.45-µm filter.

Chromatographic system

Mode: LC

Detector: UV 225 nm

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

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 1.9 × retention time of ribavirin

System suitability

Sample: Standard solution

Requirements:

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Result = (rᵤ / rₛ) × (Cₛ / L) × V × 100

Tolerances: NLT 80% (Q) dissolved.

Test 3

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

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 1: 100 rpm

Time: 30 min

Standard solution: 0.22 mg/mL of USP Ribavirin RS in Medium

Sample solution: Filter through a 0.45-µm filter

Capsule blank solution: Dissolve 6 empty Capsule shells in 900 mL Medium and filter

Instrumental conditions

Mode: UV

Analytical wavelength: 225 nm

Cell: 0.1 cm

Blank: Medium

Analysis

Samples: Standard solution, Sample solution, Capsule blank solution

Result = {[Aᵤ − (Aᵦ / 6)] / Aₛ} × Cₛ × (1 / L) × V × 100

Aᵤ = absorbance of Sample solution

Aᵦ = absorbance of Capsule blank solution

Aₛ = absorbance of Standard solution

Cₛ = concentration of Standard (mg/mL)

L = label claim (mg/Capsule)

V = 900 mL

Tolerances: NLT 80% (Q) dissolved.

Uniformity of Dosage Units 〈905〉

Meets the requirements.

5 IMPURITIES

Organic Impurities

Mobile phase, Standard solution, and Chromatographic system: Use conditions from the Assay.

Sample solution:

0.5 mg/mL ribavirin in Mobile phase

Prepare using 50 mg ribavirin from Capsules (NLT 20)

Sonicate for 20 min

Dilute to volume

Filter through a 0.45-µm filter

Analysis

Samples: Standard solution and Sample solution

Result = (rᵢ / rₛ) × (Cₛ / Cᵤ) × (1/F) × 100

rᵢ = peak response of ribose triazolole carboxylic acid or unknown impurity

rₛ = peak response of ribavirin

Cₛ = concentration of Standard (mg/mL)

Cᵤ = nominal concentration in Sample solution (mg/mL)

F = relative response factor (Table 1)

Acceptance criteria: See Table 1.

ᵃ 1-β-d-Ribofuranosyl-1H-1,2,4-triazole-3-carboxylic acid.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers; store between 15° and 30°.

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

USP Reference Standards 〈11〉

USP Ribavirin RS