Rilpivirine is a synthetic non-nucleoside reverse transcriptase inhibitor (NNRTI) used as an antiretroviral active pharmaceutical ingredient for the treatment of HIV-1 infection. The pharmaceutical API is generally supplied as Rilpivirine Hydrochloride, the monohydrochloride salt of rilpivirine.
Rilpivirine hydrochloride is used in standalone and fixed-dose antiretroviral products. Current regulatory information identifies rilpivirine hydrochloride as the active substance in Edurant and in several combination products.
Rilpivirine Hydrochloride API
PubChem and FDA-linked records confirm CAS 700361-47-3, molecular formula C₂₂H₁₉ClN₆ and molecular weight 402.9 g/mol.
Rilpivirine hydrochloride is the hydrochloride salt of rilpivirine and is characterized as a white to almost-white powder. It is practically insoluble in water over a wide pH range. The reported pKa is approximately 5.6, while the log P at pH 7 is approximately 4.86
Selected calculated molecular descriptors for the hydrochloride include:
| Parameter | Value |
|---|---|
| Molecular Weight | 402.88 g/mol |
| Exact Mass | 402.1359723 Da |
| H-Bond Donors | 3 |
| H-Bond Acceptors | 6 |
| Rotatable Bonds | 5 |
| TPSA | 97.4 Ų |
| Defined Atom Stereocenters | 0 |
| Defined Bond Stereocenters | 1 |
Rilpivirine hydrochloride exhibits polymorphism. The EMA assessment identified three polymorphic forms and several possible solvates; Form A was the routinely produced form used in manufacture of the finished product.
Rilpivirine Hydrochloride API is used in pharmaceutical products for:
The current EMA information lists rilpivirine hydrochloride as the active substance in Edurant and indicates its use with other antiretroviral medicines for HIV-1 infection.
The oral rilpivirine product contains 27.5 mg rilpivirine hydrochloride equivalent to 25 mg rilpivirine per tablet.
Rilpivirine is a diaryl-pyrimidine NNRTI that inhibits HIV-1 reverse transcriptase.
It binds to an allosteric pocket adjacent to the catalytic site of HIV-1 reverse transcriptase, producing conformational changes that inhibit the enzyme's RNA-dependent and DNA-dependent DNA polymerase activities.
By inhibiting reverse transcriptase, rilpivirine prevents conversion of viral RNA into DNA, thereby interfering with HIV-1 replication.
Because NNRTIs bind to a distinct non-catalytic site, rilpivirine differs mechanistically from nucleoside/nucleotide reverse transcriptase inhibitors.
Regulatory assessment of rilpivirine hydrochloride API identifies a comprehensive drug-substance specification containing:
EMA confirms that these controls were part of the active-substance specification and that the manufacturing process consistently produced the intended polymorphic form.
FDA's chemistry review likewise states that the rilpivirine drug-substance specification included appearance, identity, assay, impurities, residual solvents, particle size, residue on ignition, water and heavy metals.
Rilpivirine hydrochloride is produced through a multi-step synthetic process followed by formation of the hydrochloride salt and controlled crystallization.
The manufacturing process requires particular attention to:
EMA documentation describes a five-step manufacturing process and identifies Form A as the routinely produced polymorphic form.
The API should be packaged in a suitable closed pharmaceutical container providing protection from moisture, contamination and light.
Regulatory stability information for rilpivirine hydrochloride supports long-term stability studies under 25°C/60% RH and 30°C/75% RH, with accelerated studies at 40°C/75% RH. The drug substance was stored in its original container to protect it from light.
For the finished oral Edurant product, current product information specifies storage below 30°C, in the original bottle and protected from light.
API storage should follow the manufacturer's validated stability specification rather than automatically copying finished-product storage conditions.
| 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% |
| Water Content | NMT 0.5% |