Ritlecitinib is a synthetic small-molecule kinase inhibitor used in the treatment of severe alopecia areata. It is an orally administered active pharmaceutical ingredient that selectively targets Janus kinase 3 (JAK3) and members of the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family.
The pharmaceutical product LITFULO contains ritlecitinib as the active moiety in the form of ritlecitinib tosylate. The FDA identifies ritlecitinib tosylate as the active ingredient used in the finished dosage form.
The free active moiety, Ritlecitinib, has the molecular formula C₁₅H₁₉N₅O and molecular weight 285.34 g/mol. Its FDA-registered CAS number is 1792180-81-4.
For pharmaceutical manufacturing, it is important to distinguish Ritlecitinib from Ritlecitinib Tosylate.
The FDA substance hierarchy identifies Ritlecitinib as the parent active moiety and Ritlecitinib Tosylate as an active-form salt. Ritlecitinib Tosylate has the molecular formula C₂₂H₂₇N₅O₄S and molecular weight 457.55 g/mol. Its CAS number is 2192215-81-7.
The FDA-approved finished product contains 80.13 mg of ritlecitinib tosylate equivalent to 50 mg of ritlecitinib per 50 mg capsule.
| Property | Ritlecitinib | Ritlecitinib Tosylate |
|---|---|---|
| API / Active Moiety | Ritlecitinib | Ritlecitinib tosylate |
| CAS Number | 1792180-81-4 | 2192215-81-7 |
| Molecular Formula | C₁₅H₁₉N₅O | C₂₂H₂₇N₅O₄S |
| Molecular Weight | 285.34 g/mol | 457.55 g/mol |
| FDA UNII | 2OYE00PC25 | EAG4T1459K |
| PubChem CID | 118115473 | — |
| Development Code | PF-06651600 | PF-06651600 Tosylate |
| Pharmacological Class | Kinase inhibitor | Kinase inhibitor |
| Primary Targets | JAK3 and TEC family kinases | JAK3 and TEC family kinases |
| Therapeutic Area | Dermatology / Immunology | Dermatology / Immunology |
| Physical Form | — | White to off-white to pale pink solid |
| Water Solubility | — | Freely soluble in water |
FDA and PubChem records support the chemical identity of the free active moiety, while FDA labeling and the FDA substance registry establish the tosylate salt used in the pharmaceutical product.
Ritlecitinib is used as an active pharmaceutical ingredient for the treatment of severe alopecia areata.
The approved oral product is indicated for adults and pediatric patients 12 years of age and older with severe alopecia areata. The current U.S. product is marketed as LITFULO capsules.
Ritlecitinib is particularly significant among targeted dermatological therapies because its mechanism is directed at JAK3 and TEC-family kinase signaling involved in immune-cell activation.
Ritlecitinib is an irreversible kinase inhibitor. It inhibits JAK3 and the TEC kinase family by blocking their ATP-binding sites.
In cellular systems, inhibition of JAK3 reduces cytokine-induced STAT phosphorylation mediated through JAK3-dependent receptors. Ritlecitinib also inhibits signaling through immune receptors that depend on TEC-family kinases.
This targeted kinase inhibition modifies immune signaling pathways associated with the inflammatory and autoimmune processes involved in alopecia areata.
Ritlecitinib tosylate is a specialized pharmaceutical active substance requiring comprehensive analytical characterization.
The European Medicines Agency assessment report states that the active-substance specification includes:
The EMA also states that analytical methods were appropriately validated and that X-ray diffraction was used to establish crystal form.
These tests are particularly important because Ritlecitinib contains defined stereochemistry and is manufactured as the tosylate salt.
Ritlecitinib API manufacturing involves controlled chemical synthesis followed by purification, salt formation, crystallization and drying. Manufacturing controls are required to maintain chemical identity, stereochemical integrity and control process-related impurities.
For Ritlecitinib Tosylate, control of the tosylate counter-ion, chiral identity, organic impurities, residual solvents, water and particle-size distribution can be important elements of the active-substance quality strategy.
A pharmaceutical-grade manufacturing process should operate under suitable GMP controls with validated analytical methods and documented batch-release procedures.
Ritlecitinib free base has a molecular weight of 285.34 g/mol, whereas the tosylate salt used in LITFULO has a molecular weight of 457.55 g/mol.
The FDA describes Ritlecitinib Tosylate as a white to off-white to pale pink solid that is freely soluble in water. FDA's chemistry review also notes its high solubility across the physiological pH range of pH 1.0 to 6.8.
These properties support its development as an oral pharmaceutical active ingredient.
Ritlecitinib API should be packaged in appropriate pharmaceutical-grade containers that protect the material from contamination, moisture and unsuitable environmental exposure.
The EMA assessment report states that Ritlecitinib Tosylate active substance is packaged in two sealed LDPE anti-static liners and subsequently placed in an HDPE drum.
Bulk API storage should follow validated stability data and the applicable approved active-substance specification.
Pharmaceutical-grade Ritlecitinib API can be supported with appropriate quality and regulatory documentation, including:
Ritlecitinib is a specialized targeted kinase-inhibitor API requiring careful control of chemical identity, stereochemistry, salt form, impurities and physical properties.
A quality-focused Ritlecitinib API manufacturer in India should maintain validated analytical methods, controlled synthesis and purification processes, appropriate salt-form management and comprehensive quality documentation.
For Ritlecitinib Tosylate, particular attention should be given to chiral identity, assay, related substances, water, residual solvents, counter-ion content and particle-size distribution, consistent with the active-substance quality approach described by the EMA.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |