Panobinostat API Manufacturer in India

Swapnroop Pharma · WHO-GMP Certified · +91 87670 62101

Panobinostat API is a synthetic small-molecule histone deacetylase (HDAC) inhibitor belonging to the hydroxamic-acid class of pharmaceutical compounds. It is also known by the development codes LBH589 and NVP-LBH589. Panobinostat has been developed for oncology applications because of its ability to inhibit HDAC enzymes involved in chromatin remodeling, gene transcription, cell-cycle regulation and cellular survival.

Panobinostat API has the CAS Number 404950-80-7, molecular formula C₂₁H₂₃N₃O₂, and molecular weight 349.43 g/mol. FDA Global Substance Registration System and PubChem identify CAS 404950-80-7 as Panobinostat, while PubChem identifies it as a hydroxamic acid and HDAC inhibitor.

The pharmaceutical product Farydak used panobinostat lactate anhydrous as the drug substance. Panobinostat lactate anhydrous has the molecular formula C₂₁H₂₃N₃O₂·C₃H₆O₃ and molecular weight 439.51 g/mol, while the corresponding free-base equivalent is 349.43 g/mol. FDA describes panobinostat lactate anhydrous as a stable crystalline material that is slightly soluble in water and light sensitive.

Chemical Characteristics

  • Product Name: Panobinostat
  • API Name: Panobinostat API
  • CAS Number: 404950-80-7
  • Molecular Formula: C₂₁H₂₃N₃O₂
  • Molecular Weight: 349.43 g/mol
  • Development Code: LBH589
  • Alternative Development Code: NVP-LBH589
  • IUPAC Name: (E)-N-hydroxy-3-[4-[[2-(2-methyl-1H-indol-3-yl)ethylamino]methyl]phenyl]prop-2-enamide
  • UNII: 9647FM7Y3Z
  • PubChem CID: 6918837
  • ChEBI: CHEBI:85990
  • ChEMBL: CHEMBL483254
  • Chemical Class: Hydroxamic acid
  • Pharmacological Class: Histone deacetylase inhibitor
  • Physical Form: Solid
  • Stereochemistry: Achiral
  • Defined Stereocenters: 0
  • E/Z Configuration: E configuration 

Pharmacological Class

Panobinostat is a pan-HDAC inhibitor. Histone deacetylases remove acetyl groups from histone and selected non-histone proteins. Inhibition of these enzymes increases protein acetylation and modifies chromatin structure and gene transcription.

Panobinostat inhibits HDAC activity at nanomolar concentrations and affects multiple HDAC classes. FDA describes Farydak as a histone deacetylase inhibitor whose pharmacological effect is associated with increased acetylation of histone proteins.

Mechanism of Action

Panobinostat Pharmaceutical API acts by inhibiting histone deacetylase enzymes. HDAC inhibition increases acetylation of histones, producing changes in chromatin organization and transcriptional activity. These effects can influence cell-cycle progression, differentiation and apoptosis.

The compound has therefore been investigated particularly in hematological malignancies and multiple myeloma. FDA approved panobinostat in combination with bortezomib and dexamethasone for certain patients with multiple myeloma who had received at least two prior regimens, including bortezomib and an immunomodulatory agent.

Pharmaceutical Applications

Panobinostat API is primarily associated with oncology pharmaceutical development. Its best-established clinical application has been in multiple myeloma, where panobinostat was used in combination therapy.

FDA's orphan-drug database records the original Farydak marketing approval on February 23, 2015. The approved indication was combination treatment with bortezomib and dexamethasone in patients with multiple myeloma who had received at least two previous regimens.

Panobinostat has also been studied in other hematological cancers and solid tumors because HDAC inhibition affects several cellular pathways involved in malignant-cell growth and survival.

Panobinostat Lactate

For pharmaceutical API identification, it is important to distinguish Panobinostat free base from Panobinostat Lactate.

  • Panobinostat free base CAS: 404950-80-7
  • Panobinostat free-base molecular weight: 349.43 g/mol
  • Panobinostat lactate anhydrous: molecular weight 439.51 g/mol
  • Free-base equivalent in lactate: 349.43 g/mol

FDA identifies panobinostat lactate anhydrous as the drug substance used in Farydak capsules. The lactate salt is slightly soluble in water, and its solubility is pH dependent, with the highest reported solubility in citrate buffer at pH 3.0.

Physical Properties

Panobinostat is a solid crystalline compound. FDA describes the lactate anhydrous drug substance as a white to slightly yellowish or brownish powder and states that the crystalline form is chemically and thermodynamically stable with no polymorphic behavior. Panobinostat lactate anhydrous is also described as light sensitive.

Because physical appearance can vary with salt form, particle size and manufacturing process, the exact commercial API appearance should be controlled through the applicable approved specification.

Analytical Profile

Panobinostat API Supplier India quality documentation may include validated chromatographic and spectroscopic methods for identity, assay and impurity determination. HPLC or UHPLC can be used for assay and related-substance testing, while IR, LC-MS and other orthogonal techniques can support structural identification.

FDA's chemistry documentation describes analytical controls for panobinostat drug substance and drug product, including assay and impurity testing. The publicly available FDA review, however, does not provide a complete public numerical API release specification for every quality attribute.

API Quality and Impurity Control

Quality control of Panobinostat Bulk API should include appropriate controls for identity, assay, related substances, degradation products, residual solvents, elemental impurities and water, according to the approved API specification.

The numerical acceptance criteria for many Panobinostat API impurities are not publicly available in an authoritative complete monograph. Therefore, numerical limits should not be represented as USP, IP or Ph. Eur. limits unless supported by the applicable controlled specification.

Stereochemical Characteristics

Panobinostat is achiral and does not contain a stereogenic center. FDA specifically states that panobinostat free base is not chiral and shows no specific optical rotation. Therefore, a conventional enantiomeric-purity specification is not applicable to the free base.

Storage and Handling

  • Store in a tightly closed container.
  • Protect from moisture and direct light.
  • Protect from excessive heat.
  • Use suitable pharmaceutical-grade packaging.
  • Follow validated storage and retest conditions.
  • Panobinostat lactate anhydrous is reported to be light sensitive. 

Documentation for Pharmaceutical Manufacturing

A Panobinostat API Manufacturer may provide:

  • Certificate of Analysis
  • API Specification
  • HPLC/UHPLC Assay Report
  • Related Substance Profile
  • Residual Solvent Report
  • Water Content Report
  • Elemental Impurity Data
  • Analytical Method Information
  • Stability Data
  • Safety Data Sheet
  • GMP Documentation
  • Regulatory Support Documentation

Panobinostat API for Pharmaceutical Industry

Panobinostat Pharmaceutical API is relevant to manufacturers and pharmaceutical research organizations working with HDAC inhibitor products and oncology formulations. Accurate identification of the API form is essential because the free base and lactate salt have different molecular weights and physical characteristics.

For a Panobinostat API Supplier, product documentation should clearly state whether the material supplied is Panobinostat free base or Panobinostat lactate. This avoids incorrect calculation of potency, molecular weight and formulation quantities.

Detailed Specifications

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%
Heavy Metals NMT 10 ppm
pH (1% Solution) 5.0 – 7.0
Individual Impurity NMT 0.5%
Water Content NMT 0.5%
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