Nebivolol Hydrochloride, commonly abbreviated as Nebivolol HCl, is a synthetic beta-adrenergic receptor blocker (beta-blocker) active pharmaceutical ingredient (API) used primarily in the management of hypertension. It is a cardioselective β1-adrenergic receptor antagonist with additional vasodilatory activity mediated through the nitric oxide (NO) pathway.
Nebivolol HCl is the hydrochloride salt of nebivolol and is used in pharmaceutical formulation development and manufacture of oral medicines.
Nebivolol HCl is a well-characterized cardiovascular pharmaceutical API used in the development and manufacture of medicines for hypertension and related cardiovascular applications.
Important API quality attributes include identity, assay, related substances, enantiomeric purity, water content, residual solvents, elemental impurities and other applicable pharmaceutical quality parameters.
CAS Number: 152520-80-8
Molecular Formula: C22H26F2NO4 · HCl
Molecular Weight: 441.90 g/mol
Chemical Name: (1RS,1'RS)-2,2'-[(2RS,2'RS)-bis(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2-hydroxyethyl]iminodiethanol hydrochloride
Drug Class: Beta-Adrenergic Receptor Blocker
Therapeutic Class: Antihypertensive / Beta-Blocker
Therapeutic Area: Cardiovascular
Molecule Type: Synthetic Small Molecule
Nebivolol selectively blocks β1-adrenergic receptors, particularly in cardiac tissue. It also promotes vasodilatory effects through modulation of the nitric oxide pathway.
Its pharmacological activity includes:
Nebivolol has greater β1-selectivity at clinically relevant concentrations than nonselective beta-blockers.
Nebivolol HCl API is relevant to:
Nebivolol-containing medicines are primarily used for the treatment of hypertension. In some markets and formulations, nebivolol has also been used in the management of certain forms of heart failure.
The approved indication can vary according to the regulatory jurisdiction and specific formulation. Therapeutic use should therefore be based on the applicable approved prescribing information.
Nebivolol Hydrochloride is generally described as a white to off-white crystalline powder. It is the hydrochloride salt of nebivolol and has physicochemical characteristics appropriate for pharmaceutical formulation.
The API's physical properties, particle size, polymorphic characteristics and moisture content should be controlled according to the applicable pharmaceutical specification.
Stereochemistry is particularly important for Nebivolol HCl because nebivolol contains multiple stereogenic centers and is associated with a mixture of stereoisomeric components.
The marketed pharmaceutical substance is characterized by defined stereochemical composition. Therefore, enantiomeric/diastereomeric purity and stereochemical identity are important quality considerations during API manufacturing and release testing.
A controlled Nebivolol HCl API manufacturing process may involve:
The actual commercial manufacturing route should be based on the manufacturer's validated process and regulatory documentation.
Typical Nebivolol HCl API testing may include:
Assay testing is used to determine the content of Nebivolol HCl using a validated analytical procedure.
Related-substance testing is important for controlling process-related impurities and degradation products. Because Nebivolol is a stereochemically complex molecule, stereoisomeric purity is also an important aspect of pharmaceutical quality control.
Numerical acceptance criteria should be aligned with the applicable current pharmacopoeial standard or approved API specification.
Nebivolol HCl is relevant to research involving:
Store Nebivolol HCl API in a tightly closed container under controlled pharmaceutical storage conditions, protected from excessive moisture, heat and direct light.
The final storage temperature and packaging requirements should be established according to validated stability data and the applicable API specification.
Nebivolol HCl intended for pharmaceutical manufacture should be produced and tested under applicable GMP requirements.
Critical quality attributes include identity, assay, purity, stereochemical composition, residual solvents, water content and elemental impurities.
The exact release criteria should be taken from the current applicable pharmacopoeial monograph or approved manufacturer specification.
| Parameter | Specification |
|---|---|
| Appearance | White crystalline powder or crystals |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 2.0% |
| Water Content | NMT 1.0% |
| Melting Point | Approximately 223–225°C |