Ribavirin for Inhalation Solution

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 for Inhalation Solution is a sterile, freeze-dried form of ribavirin. When constituted as directed in the labeling, the inhalation solution so obtained contains NLT 95.0% and NMT 105.0% of the labeled amount of ribavirin (C₈H₁₂N₄O₅).

2 IDENTIFICATION

Change to read:

A. ▲Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K▲ (CN 1-May-2020)

B. Thin-Layer Chromatographic Identification Test 〈201〉

Sample solution: 10 mg/mL

Chromatographic system

Developing solvent system: Acetonitrile and 0.1 M ammonium chloride (9:2)

Spray reagent: Anisaldehyde, alcohol, glacial acetic acid, and sulfuric acid (5:90:1:5)

Analysis:

Proceed as directed in the chapter. Allow the plate to air-dry for about 15 min, spray with Spray reagent, heat the plate at 110° for 30 min, and locate the spots on the plate by examining the plate in daylight.

Acceptance criteria: Meets the requirements

3 ASSAY

Procedure

Mobile phase:

Adjust water with sulfuric acid to a pH of 2.5 ± 0.1. Filter through a suitable filter of 0.5-µm or finer pore size.

Standard solution:

0.025 mg/mL of USP Ribavirin RS in Mobile phase

Sample stock solution:

Constitute Ribavirin for Inhalation Solution as directed in the labeling, using a suitable volume of diluent. Transfer an aliquot of constituted solution, equivalent to 100 mg of ribavirin, to a 200-mL volumetric flask, and dilute with Mobile phase to volume.

Sample solution:

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

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 207 nm

Column: 7.8-mm × 10-cm; packing L17

Column temperature: 65 ± 0.5°

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 0.5%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ribavirin (C₈H₁₂N₄O₅) in the portion of Ribavirin for Inhalation Solution 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: 95.0%–105.0%

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.25%

Organic Impurities

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

Sample solution: Prepare as directed for the Sample stock solution in the Assay.

Analysis

Sample: Sample stock solution

Calculate the percentage of each peak, other than that of the solvent peak and the ribavirin peak, in the portion of Ribavirin for Inhalation Solution taken:

Result = (rᵢ / rₜ) × 100

rᵢ = response of the individual peak

rₜ = sum of all the peak responses

Acceptance criteria

— Individual impurity: NMT 0.25%

— Total impurities: NMT 1.0%

5 SPECIFIC TESTS

Sterility Tests 〈71〉:

Meets the requirements when tested as directed in Test for Sterility of the Product to Be Examined, Membrane Filtration.

Optical Rotation, Specific Rotation 〈781S〉

Sample solution: 10 mg/mL

Acceptance criteria: −33.5° to −37.0° (t = 20°)

pH 〈791〉

Sample solution: A solution constituted as directed in the labeling. To each 50 mL of reconstituted solution add 0.2 mL of a saturated potassium chloride solution.

Acceptance criteria: 4.0–6.5

Loss on Drying 〈731〉

Analysis: Dry a sample at 105° for 5 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage:

Preserve in tight containers, in a dry place at controlled room temperature.

Labeling:

The labeling indicates that Ribavirin for Inhalation Solution must be constituted with a measured volume of Sterile Water for Injection or with Sterile Water for Inhalation containing no preservatives, and that the constituted solution is to be administered only by a small-particle aerosol generator.

USP Reference Standards 〈11〉

USP Ribavirin RS