Nintedanib Esylate API Manufacturer in India

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Nintedanib Esylate API

Nintedanib Esylate is the ethanesulfonate salt of Nintedanib, a small-molecule multi-target tyrosine kinase inhibitor used in pharmaceutical formulations for the treatment of idiopathic pulmonary fibrosis (IPF) and certain cancers. Nintedanib inhibits multiple receptor tyrosine kinases, including VEGFR, FGFR and PDGFR, as well as other kinases involved in angiogenesis, fibrosis and tumor progression.

Nintedanib Esylate is an important antifibrotic and antineoplastic pharmaceutical API for research, formulation development and manufacture of oral solid dosage formulations.

Nintedanib Esylate API Manufacturer in India

Nintedanib Esylate is a specialized pharmaceutical active ingredient used in the development and manufacture of medicines targeting fibrotic lung diseases and oncology indications.

The esylate salt improves the pharmaceutical properties of Nintedanib and is the form used in marketed Nintedanib capsule formulations. EMA identifies the active substance as nintedanib esylate and describes its molecular mass as 649.76 g/mol.

Chemical Information

CAS Number: 656247-18-6

Molecular Formula: C₃₃H₃₉N₅O₇S

Molecular Weight: 649.76 g/mol

Chemical Name: Nintedanib ethanesulfonate

Salt Form: 1:1 ethanesulfonate salt

Synonym: BIBF 1120 esylate

Drug Class: Tyrosine Kinase Inhibitor

Therapeutic Class: Antifibrotic / Antineoplastic Agent

Therapeutic Area: Respiratory Diseases / Oncology

Molecule Type: Synthetic Small Molecule

Target Class: Receptor Tyrosine Kinases and Non-Receptor Tyrosine Kinases

PubChem identifies Nintedanib Esylate as CAS 656247-18-6 with molecular formula C₃₃H₃₉N₅O₇S and molecular weight approximately 649.8 g/mol.

Mechanism of Action

Nintedanib is a multi-target tyrosine kinase inhibitor. It inhibits receptor tyrosine kinases involved in angiogenesis, fibrosis and cellular signaling.

Important targets include:

  • Vascular endothelial growth factor receptors VEGFR-1, VEGFR-2 and VEGFR-3
  • Fibroblast growth factor receptors FGFR-1, FGFR-2 and FGFR-3
  • Platelet-derived growth factor receptors PDGFR-α and PDGFR-β
  • Fms-like tyrosine kinase-3 (FLT3)
  • Other signaling kinases involved in cellular proliferation and migration

Through inhibition of these pathways, Nintedanib can interfere with angiogenic signaling and fibroblast-related processes.

Pharmaceutical Applications

Nintedanib Esylate API is relevant to:

  • Idiopathic pulmonary fibrosis formulations
  • Progressive fibrosing interstitial lung disease formulations
  • Systemic-sclerosis-associated interstitial lung disease
  • Oncology drug development
  • Tyrosine kinase inhibitor research
  • Antifibrotic drug development
  • Angiogenesis research
  • Fibroblast growth factor signaling research
  • Pharmaceutical formulation development
  • API analytical research

Respiratory Disease Applications

Nintedanib is used therapeutically in formulations for idiopathic pulmonary fibrosis and other approved fibrosing interstitial lung diseases. Its antifibrotic activity is associated with inhibition of growth-factor receptor signaling involved in fibroblast activation and fibrosis.

Oncology Applications

Nintedanib also has applications in oncology. Its inhibition of VEGFR, FGFR and PDGFR signaling makes it relevant to research involving tumor angiogenesis and cancer-cell signaling.

Its exact approved indications depend on the regulatory jurisdiction and specific formulation.

Physical Characteristics

Nintedanib Esylate is described in U.S. regulatory labeling as a greenish-yellow to bright-yellow powder. The FDA documentation identifies its empirical formula as C₃₁H₃₃N₅O₄·C₂H₆O₃S and molecular weight as 649.76 g/mol.

Solubility

Nintedanib Esylate has limited aqueous solubility, although its salt form has improved aqueous properties compared with the free base. A published solubility study specifically investigated Nintedanib Esylate hemihydrate and reported that solubility varies significantly with solvent and temperature.

For CMS purposes, a useful reported value is approximately 2.8 mg/mL in water at around pH 5.7, although this is a literature/reference solubility value rather than a pharmaceutical release specification.

Manufacturing Process

A controlled Nintedanib Esylate API manufacturing process may involve:

  1. Qualification of starting materials
  2. Preparation of Nintedanib free-base intermediate
  3. Controlled purification
  4. Reaction with ethanesulfonic acid
  5. Formation of Nintedanib ethanesulfonate
  6. Controlled crystallization
  7. Solid-form control
  8. Filtration
  9. Washing
  10. Controlled drying
  11. Milling, where required
  12. Particle-size control
  13. Final analytical testing
  14. GMP-compliant packaging

Quality Control Testing

Typical Nintedanib Esylate API quality-control testing may include:

  • Identification by IR
  • HPLC identification
  • Assay by HPLC
  • Related substances
  • Individual impurities
  • Total impurities
  • Water content
  • Loss on drying
  • Residual solvents
  • Heavy metals / elemental impurities
  • pH of specified solution
  • Solid-state / polymorphic characterization
  • Particle-size distribution
  • Stability testing

Because Nintedanib Esylate can occur in different solid forms, solid-form and water-content control can be particularly important. Research has identified Nintedanib Esylate hemihydrate as a distinct crystalline form containing approximately half a molecule of water.

Storage

Store Nintedanib Esylate API in a tightly closed container under controlled pharmaceutical storage conditions, protected from excessive moisture, heat and direct light.

The exact commercial storage condition should follow the validated stability data and applicable API specification.

Detailed Specifications

Parameter Specification
Appearance White crystalline powder or crystals
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 – 10.0
Individual Impurity NMT 0.5%
Total Impurities NMT 1.0%
Water Content NMT 5.0%
Melting Point >233°C (decomposition reported)
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