Ribavirin is a synthetic nucleoside analogue antiviral API structurally related to guanosine. It is a 1-β-D-ribofuranosyl derivative of 1,2,4-triazole-3-carboxamide and has been used in antiviral pharmaceutical formulations. PubChem identifies Ribavirin as CAS 36791-04-5, molecular formula C₈H₁₂N₄O₅, and molecular weight 244.20 g/mol.
Ribavirin has been incorporated into oral and inhalation pharmaceutical products. Current U.S. labeling includes ribavirin capsules for use in combination with interferon alfa-2b for chronic hepatitis C, while ribavirin inhalation solution has been used for respiratory syncytial virus (RSV) infection.
Ribavirin is a 1-ribosyltriazole nucleoside analogue containing a triazole carboxamide moiety attached to a D-ribofuranose ring. Its IUPAC name is:
1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxamide.
PubChem reports an exact mass of 244.08076950 Da, XLogP3 of −1.8, hydrogen-bond donor count of 4, hydrogen-bond acceptor count of 7, 3 rotatable bonds, and topological polar surface area of 144 Ų.
Ribavirin exhibits polymorphism. Pharmacopoeial information describes it as a white or almost white crystalline powder and notes that it is freely soluble in water.
Ribavirin is an antiviral API used in pharmaceutical products for specific viral infections.
Current U.S. labeling for ribavirin capsules describes its use in combination with pegylated or non-pegylated interferon alfa-2b for treatment of chronic hepatitis C in patients aged 3 years and older with compensated liver disease. The label specifically states that ribavirin monotherapy is not effective for chronic hepatitis C.
Ribavirin has also been formulated as a sterile lyophilized powder for inhalation. DailyMed describes a 6 g vial for preparation of inhalation solution using a small-particle aerosol generator.
Ribavirin is a nucleoside analogue whose antiviral activity is complex and involves intracellular phosphorylation to active ribavirin phosphate metabolites. Its mechanisms have been described as including interference with viral RNA metabolism and synthesis, inhibition of inosine monophosphate dehydrogenase and modulation of immune responses.
Ribavirin triphosphate is a recognized intracellular metabolite and is structurally related to nucleotide triphosphates involved in nucleic-acid metabolism.
The precise contribution of individual mechanisms varies according to the virus and treatment context; therefore, Ribavirin should not be represented as acting through a single universal antiviral mechanism.
Quality control for Ribavirin API may include:
The European Pharmacopoeia monograph identifies Ribavirin as containing 98.0% to 102.0% of Ribavirin calculated on the dried substance. It specifies a white or almost white crystalline powder, pH 4.0–6.5, and specific optical rotation of −33 to −37 on the dried substance.
A pharmacopoeial source also identifies Ribavirin as freely soluble in water, slightly soluble in ethanol and slightly or very slightly soluble in methylene chloride.
Ribavirin is a synthetic nucleoside analogue API manufactured through controlled chemical synthesis followed by purification and crystallization. Manufacturing controls should ensure consistent stereochemical identity of the ribofuranosyl portion, chemical purity and control of related substances.
Because Ribavirin exhibits polymorphism, control of the solid-state form may also be relevant during API manufacturing and pharmaceutical formulation.
Chemical descriptors are from PubChem, while pH, appearance, solubility and optical rotation values are supported by pharmacopoeial information.
Bulk Ribavirin API should be packaged in a suitable pharmaceutical-grade, well-closed container that protects the material from contamination and environmental exposure.
For the finished oral product, DailyMed specifies storage at 20–25°C, with excursions permitted to 15–30°C, and the bottle should be kept tightly closed.
Bulk API storage should ultimately follow validated stability data and the applicable API specification.
Typical documentation for Ribavirin API may include:
A qualified Ribavirin API manufacturer in India should maintain robust controls over synthetic processing, purification, crystalline form, assay and impurity management.
For Ribavirin, pharmacopoeial controls such as 98.0–102.0% assay on the dried basis, pH 4.0–6.5 and specific optical rotation −33 to −37° provide useful objective quality parameters for pharmaceutical API characterization.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| pH (1% Solution) | 4.0–6.5 |