Riociguat is a synthetic small-molecule active pharmaceutical ingredient belonging to the class of soluble guanylate cyclase (sGC) stimulators. It is used in pharmaceutical formulations for the treatment of pulmonary vascular diseases, particularly pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH).
Riociguat has the molecular formula C₂₀H₁₉FN₈O₂ and a molecular weight of 422.42 g/mol. Its CAS Registry Number is 625115-55-1. USP-NF has an official monograph for Riociguat and specifies an assay range of 98.0–102.0%, calculated on a solvent-free basis.
Riociguat is a heterocyclic pharmaceutical compound containing aminopyrimidine and pyrazolopyridine structural features together with a fluorobenzyl group and methylcarbamate functionality.
The API is described in the FDA prescribing information as a white to yellowish, crystalline, non-hygroscopic substance. It is stable to temperature, light and humidity in solid form.
Riociguat is principally supplied as the active pharmaceutical ingredient for oral solid dosage formulations. Its physicochemical characteristics, including limited aqueous solubility and pH-dependent solubility, are important considerations during formulation development.
| Property | Riociguat |
|---|---|
| API Name | Riociguat |
| CAS Number | 625115-55-1 |
| Molecular Formula | C₂₀H₁₉FN₈O₂ |
| Molecular Weight | 422.42 g/mol |
| PubChem CID | 11304743 |
| UNII | RU3FE2Y4XI |
| ChEBI ID | CHEBI:76018 |
| API Class | Small-molecule sGC stimulator |
| Pharmacological Class | Soluble guanylate cyclase stimulator |
| Physical Form | White to yellowish crystalline substance |
| Hygroscopicity | Non-hygroscopic |
| USP Assay | 98.0–102.0%, solvent-free basis |
The chemical identity and molecular characteristics are supported by PubChem, while the USP-NF monograph confirms the official assay range.
Riociguat is used in pharmaceutical products for two major pulmonary hypertension indications.
It is indicated for adults with persistent or recurrent CTEPH after surgical treatment or inoperable CTEPH, where it is used to improve exercise capacity and WHO functional class.
It is also indicated for adults with pulmonary arterial hypertension (PAH), WHO Group 1, where treatment is intended to improve exercise capacity and functional class and delay clinical worsening.
Riociguat has therefore become an important API for pharmaceutical development involving pulmonary hypertension therapies.
Riociguat acts as a soluble guanylate cyclase stimulator. Soluble guanylate cyclase is an important receptor/enzyme in the nitric oxide (NO) signaling pathway.
Riociguat has a dual mechanism. It sensitizes soluble guanylate cyclase to endogenous nitric oxide by stabilizing NO-sGC interaction and also directly stimulates sGC through a separate binding site independently of nitric oxide.
Activation of this pathway increases intracellular cyclic guanosine monophosphate (cGMP). Increased cGMP promotes vascular smooth-muscle relaxation and vasodilation, helping to improve pulmonary vascular function.
Riociguat is covered by a USP-NF drug-substance monograph. The USP definition requires the API to contain NLT 98.0% and NMT 102.0% Riociguat, calculated on a solvent-free basis.
Quality evaluation of Riociguat API may include:
The specific numerical acceptance criteria for individual quality attributes should be taken from the applicable current specification rather than assumed from generic API practices.
Riociguat API manufacturing involves controlled multi-step chemical synthesis followed by purification, isolation and drying. Manufacturing controls are particularly important for controlling process-related impurities, residual solvents and related substances.
A pharmaceutical-grade manufacturing process should incorporate appropriate GMP controls, validated analytical procedures, controlled raw materials and documented batch-release testing.
Process consistency is important because Riociguat is used as an active pharmaceutical ingredient in regulated oral pharmaceutical products.
Riociguat is a white to yellowish, crystalline, non-hygroscopic substance. The FDA reports a molecular weight of 422.42 g/mol and describes the solid form as stable to temperature, light and humidity.
Its aqueous solubility is relatively low and exhibits strong pH dependence. At 25°C, the FDA label reports approximately 4 mg/L in water, 800 mg/L in ethanol, 250 mg/L in 0.1 N HCl at pH 1, and 3 mg/L in phosphate buffer at pH 7. Solubility increases substantially under acidic conditions between pH 2 and 4.
These characteristics are important in pharmaceutical formulation and dissolution development.
Riociguat API should be packaged in suitable pharmaceutical-grade containers that protect the material from contamination, moisture and inappropriate environmental exposure.
The FDA describes solid Riociguat as non-hygroscopic and stable to temperature, light and humidity. Nevertheless, API packaging and storage should follow the validated manufacturer stability program and applicable approved specification.
Suitable packaging should maintain product integrity during storage and transportation and provide complete batch traceability.
Pharmaceutical-grade Riociguat API can be supported with appropriate quality and regulatory documentation, depending on the customer's requirements:
Riociguat is a specialized pharmaceutical API requiring controlled synthesis, impurity management and reliable analytical characterization. A quality-focused Riociguat API manufacturer in India should maintain appropriate manufacturing controls and analytical systems to provide consistent pharmaceutical-grade material.
The USP-NF monograph provides a verified assay requirement of 98.0–102.0% on a solvent-free basis, providing an established benchmark for drug-substance quality.
Reliable manufacturing, controlled impurity profiles, appropriate packaging and comprehensive quality documentation are important considerations for pharmaceutical companies sourcing Riociguat API for regulated product development and manufacturing.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |