Tenofovir Alafenamide Fumarate API is a nucleotide reverse transcriptase inhibitor (NRTI) prodrug of tenofovir. It is used as an active pharmaceutical ingredient in antiretroviral and antiviral medicines. Tenofovir alafenamide is converted intracellularly to tenofovir diphosphate, the active metabolite that inhibits HIV-1 reverse transcriptase and hepatitis B virus reverse transcriptase.
Tenofovir Alafenamide Fumarate is commonly described as the hemifumarate (2:1) salt, consisting of two molecules of tenofovir alafenamide associated with one molecule of fumaric acid. The FDA identifies the drug substance with an empirical formula of C₂₁H₂₉N₆O₅P·½(C₄H₄O₄) and a formula weight of 534.5 g/mol.
FDA labeling identifies Tenofovir Alafenamide Fumarate as a white to off-white or tan powder and reports an aqueous solubility of approximately 4.7 mg/mL at 20°C.
Tenofovir alafenamide is a phosphonamidate prodrug designed to deliver tenofovir efficiently into cells. Compared with earlier tenofovir prodrugs, its design provides intracellular delivery of the active tenofovir metabolite at relatively low systemic tenofovir exposure.
The molecule contains an adenine nucleoside analogue structure together with a phosphonamidate group and an L-alanine ester. The fumarate form is used as the pharmaceutical drug substance in several approved formulations. PubChem identifies tenofovir alafenamide as C₂₁H₂₉N₆O₅P with a molecular weight of approximately 476.5 g/mol for the free active moiety.
Tenofovir alafenamide is used in pharmaceutical products for antiviral therapy.
It is used in combination antiretroviral regimens for the treatment of HIV-1 infection and is also used for the treatment of chronic hepatitis B virus infection in appropriate patient populations and approved formulations.
Tenofovir alafenamide fumarate is incorporated into several fixed-dose combination products together with other antiviral agents. It is also marketed as a standalone tenofovir alafenamide product for chronic hepatitis B in appropriate indications.
Tenofovir alafenamide is a prodrug that is converted intracellularly to tenofovir diphosphate. Tenofovir diphosphate competes with natural deoxyribonucleotide substrates and becomes incorporated into viral DNA, resulting in inhibition of viral DNA polymerization and chain termination.
Its antiviral activity is directed against reverse transcriptase activity associated with HIV-1 and hepatitis B virus.
Quality control of Tenofovir Alafenamide Fumarate API requires analytical procedures suitable for a stereochemically defined small-molecule drug substance.
Typical API testing includes:
A regulatory assessment of Tenofovir Alafenamide Fumarate API describes controls for identity by IR, HPLC and PXRD, loss on drying, residue on ignition, heavy metals, chiral purity, residual solvents, HPLC assay, related impurities and water by Karl Fischer.
Swapnroop Drugs and Pharmaceuticals provides pharmaceutical API manufacturing capabilities for pharmaceutical development and manufacturing requirements.
Tenofovir Alafenamide Fumarate requires controlled manufacturing and analytical testing because the API contains defined stereochemistry and is sensitive to chemical and environmental conditions. Appropriate quality control focuses on identity, assay, related substances, chiral purity, water content, residual solvents and other applicable drug-substance attributes.
Tenofovir Alafenamide Fumarate API should be packaged in suitable pharmaceutical-grade, well-closed containers that protect the material from moisture, light and contamination.
Regulatory documentation for the API describes storage in tight, light-resistant containers at below 25°C for a specific approved API packaging configuration. Actual commercial storage conditions should follow the manufacturer's validated stability data and approved product specification.
Depending on customer and regulatory requirements, documentation for Tenofovir Alafenamide Fumarate API may include:
Swapnroop Drugs and Pharmaceuticals focuses on quality-oriented pharmaceutical API manufacturing with appropriate analytical controls for pharmaceutical applications.
For Tenofovir Alafenamide Fumarate, key quality attributes include chemical identity, assay, chromatographic purity, stereochemical purity, water content, residual solvents and control of process-related and degradation-related impurities.
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| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.10% |
| Heavy Metals | NMT 20 ppm |
| Individual Impurity | NMT 0.15% |
| Total Impurities | NMT 2.0% |
| Water Content | NMT 1.0% |
| Solubility | Approximately 4.7 mg/mL in water at 20°C |