Tafamidis API is a selective transthyretin (TTR) stabilizer belonging to the benzoxazole class of pharmaceutical compounds. Tafamidis is the active moiety used in medicines for transthyretin-mediated amyloidosis and is available commercially as the free acid and, in certain formulations, as tafamidis meglumine.
Tafamidis is chemically known as 2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid. It is a synthetic small-molecule API developed to stabilize the native transthyretin tetramer and reduce the formation of amyloidogenic monomers.
The API is relevant to pharmaceutical development and manufacturing programs involving transthyretin amyloidosis, particularly wild-type and hereditary transthyretin-mediated cardiomyopathy.
Tafamidis is a selective transthyretin tetramer stabilizer. It binds to the thyroxine-binding sites of transthyretin and helps prevent dissociation of the native tetramer into monomers.
The FDA identifies Tafamidis as an ingredient substance with the molecular formula C₁₄H₇Cl₂NO₃ and molecular weight 308.12 g/mol. Its CAS number is 594839-88-0 and its FDA UNII is 8FG9H9D31J.
Tafamidis is supplied as a pharmaceutical active ingredient for formulation and drug-product manufacturing under appropriate quality, analytical and regulatory controls.
| Parameter | Details |
|---|---|
| Generic Name | Tafamidis |
| API Form | Tafamidis Free Acid |
| Chemical Name | 2-(3,5-Dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid |
| CAS Number | 594839-88-0 |
| Molecular Formula | C₁₄H₇Cl₂NO₃ |
| Molecular Weight | 308.12 g/mol |
| Drug Class | Transthyretin stabilizer |
| Therapeutic Class | Amyloidosis therapy |
| Chemical Class | Benzoxazole derivative |
| FDA UNII | 8FG9H9D31J |
| Stereochemistry | No defined stereocenters |
Tafamidis has no defined stereocenters, and the active pharmaceutical substance is the free acid. Tafamidis meglumine should be treated as a separate salt form and should not be substituted for the free-acid identity in API documentation.
Tafamidis is used as an active pharmaceutical ingredient in medicines intended for the management of transthyretin-mediated amyloidosis.
Current U.S. labeling identifies tafamidis and tafamidis meglumine as transthyretin stabilizers indicated for adults with cardiomyopathy associated with wild-type or hereditary transthyretin-mediated amyloidosis, with the objective of reducing cardiovascular mortality and cardiovascular-related hospitalization.
Tafamidis has also been investigated and used clinically in hereditary transthyretin amyloidosis, including disease associated with transthyretin mutations and peripheral neurologic manifestations.
Tafamidis selectively binds to the thyroxine-binding sites of the native transthyretin tetramer. This interaction stabilizes the tetramer and slows its dissociation into monomeric transthyretin.
Tetramer dissociation is an important rate-limiting step in the amyloidogenic pathway. By reducing tetramer dissociation, tafamidis decreases the availability of misfolding-prone monomers and consequently reduces the downstream process of amyloid formation.
Tafamidis therefore acts as a kinetic stabilizer of transthyretin, rather than directly removing already deposited amyloid fibrils.
Tafamidis API quality control should include a validated analytical testing program appropriate for pharmaceutical manufacturing.
Typical quality-control parameters include:
The FDA regulatory review notes that Tafamidis drug substance is crystalline and that particle size was considered a critical quality attribute because of the low solubility of the drug substance.
All release specifications should be established against the applicable customer specification, validated analytical methods and current regulatory requirements rather than relying on non-pharmaceutical research-product specifications.
Tafamidis API manufacturing involves controlled chemical synthesis followed by purification, isolation and appropriate solid-state processing to obtain pharmaceutical-quality material.
Manufacturing controls may include:
A pharmaceutical-grade Tafamidis API manufacturing process should be supported by appropriate analytical documentation and quality systems.
Tafamidis API should be packed in suitable pharmaceutical-grade containers that protect the material from moisture, contamination and unsuitable environmental exposure.
Recommended storage should follow the manufacturer's validated stability data and approved API specification. Containers should remain tightly closed and be stored under controlled temperature and humidity conditions.
The recommended storage conditions for a particular commercial batch should always be confirmed from the current Certificate of Analysis, specification and stability documentation.
Documentation available for Tafamidis API can include:
Choosing a reliable Tafamidis API Manufacturer in India supports consistent pharmaceutical manufacturing, controlled quality and dependable supply of the active pharmaceutical ingredient.
A professional manufacturing and supply program should focus on:
Swapnroop focuses on providing pharmaceutical API solutions supported by quality-oriented manufacturing, analytical control and documentation for pharmaceutical development and commercial requirements.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |