Raltegravir API Manufacturer in India

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Raltegravir API Manufacturer in India

Raltegravir is an HIV-1 integrase strand transfer inhibitor (INSTI) used in combination with other antiretroviral medicines for the treatment of HIV-1 infection. It was the first drug of the integrase inhibitor class to receive FDA approval and is marketed as raltegravir potassium

The pharmaceutical API is raltegravir potassium, CAS No. 871038-72-1, with the molecular formula C20H20FKN6O5 and molecular weight 482.51 g/mol. The potassium salt is the form used in marketed raltegravir products such as Isentress. 

Raltegravir API

Raltegravir is a synthetic small-molecule antiviral API belonging to the HIV integrase inhibitor class. The active pharmaceutical form is generally supplied as raltegravir potassium.

Raltegravir inhibits HIV-1 integrase, an essential viral enzyme responsible for integrating viral DNA into the host-cell genome. By inhibiting the strand-transfer step of viral DNA integration, raltegravir prevents productive HIV replication. 

Raltegravir itself is the free phenolic active moiety, while raltegravir potassium is its monopotassium salt. The marketed 400 mg tablet contains 434.4 mg raltegravir potassium equivalent to 400 mg raltegravir

Chemical and Pharmaceutical Profile

ParameterDetails
Product NameRaltegravir Potassium
Active MoietyRaltegravir
SynonymMK-0518
CAS Number871038-72-1
Free Raltegravir CAS518048-05-0
Molecular FormulaC20H20FKN6O5
Molecular Weight482.51 g/mol
PubChem CID23668479
Free Raltegravir CID54671008
UNII – Active Moiety22VKV8053U
Drug ClassHIV-1 Integrase Strand Transfer Inhibitor
Therapeutic ClassAntiretroviral / Antiviral
Therapeutic AreaHIV / Infectious Diseases
API TypeSynthetic small-molecule API
Salt FormMonopotassium salt
StereochemistryAchiral

PubChem reports raltegravir potassium as C20H20FKN6O5 with a molecular weight of 482.5 g/mol and CAS 871038-72-1.

The current DailyMed labeling identifies the pharmaceutical substance as raltegravir potassium and gives the molecular weight as 482.51 g/mol. (dailymed.nlm.nih.gov)

Pharmacological Class

Raltegravir belongs to the HIV-1 integrase strand transfer inhibitor (INSTI) class of antiretroviral medicines.

It inhibits HIV integrase, which is required for insertion of viral DNA into the DNA of infected human cells. Raltegravir is administered as part of combination antiretroviral therapy rather than as monotherapy. (pubchem.ncbi.nlm.nih.gov)

Mechanism of Action

Raltegravir selectively inhibits the catalytic activity of HIV-1 integrase.

Following reverse transcription of HIV RNA, the resulting viral DNA must be integrated into the host-cell genome for productive infection. Raltegravir binds to the integrase active site and inhibits the strand-transfer reaction required for viral DNA integration.

This results in:

  • Inhibition of HIV-1 DNA integration
  • Prevention of productive viral replication
  • Reduction of HIV viral replication when used with other antiretroviral agents

Raltegravir therefore acts at a stage of the HIV replication cycle distinct from reverse-transcriptase and protease inhibitors. (pubchem.ncbi.nlm.nih.gov)

Pharmaceutical Applications

Raltegravir potassium is primarily used as an antiretroviral API.

Documented pharmaceutical applications include:

  • Treatment of HIV-1 infection
  • Combination antiretroviral therapy
  • Treatment of HIV-1 infection in adults
  • Treatment of HIV-1 infection in pediatric patients meeting applicable age/weight requirements
  • Development of immediate-release tablets
  • Development of chewable tablets
  • Development of oral-suspension granules
  • HIV integrase inhibitor research
  • Pharmaceutical and bioanalytical research

WHO lists raltegravir among antiretroviral medicines in the integrase inhibitor class, including oral tablet and oral-suspension formulations. 

Current U.S. labeling includes film-coated tablets, chewable tablets and granules for oral suspension, with dosing dependent on formulation and patient population. 

Quality and Analytical Testing

Raltegravir potassium is a synthetic small-molecule API for which pharmacopoeial quality-control procedures are available.

Appropriate analytical characterization may include:

  • Infrared spectroscopy
  • HPLC assay
  • HPLC related-substance analysis
  • Water determination
  • Chromatographic identification
  • UV detection
  • Residual-solvent testing
  • Elemental impurity testing
  • Solid-state characterization
  • Stability-indicating analysis

The USP monograph identifies IR spectroscopy and chromatographic retention time as identification procedures. Its assay uses liquid chromatography with UV detection at 220 nm

The USP chromatographic system specifies an L11 column, 4.6 mm × 15 cm, 3.5 µm, with a flow rate of 1.0 mL/min and column temperature of 15°C. System suitability includes a tailing factor of NMT 1.5 and relative standard deviation of NMT 1.0%.

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%
Individual Impurity NMT 0.10%
Total Impurities NMT 0.50%
Water Content NMT 0.6%.
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