Baricitinib is a synthetic, selective inhibitor of Janus kinases JAK1 and JAK2, engineered for advanced pharmaceutical formulation development and commercial drug manufacturing. Supplied as a white to off-white crystalline powder, it modulates intracellular signaling pathways involved in inflammatory and autoimmune responses. Produced under strict synthetic controls to minimize genotoxic impurities and residual catalysts, this active pharmaceutical ingredient ensures compatibility with solid oral dosage manufacturing lines and supports stringent regulatory filing submissions.
Specifications & Physico-Chemical Properties
|
Parameter |
Specification |
|
International Nonproprietary Name |
Baricitinib |
|
CAS Registry Number |
1187594-09-7 |
|
Chemical Name |
2-[1-ethylsulfonyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]azetidin-3-yl]acetonitrile |
|
Physical Description |
White to off-white crystalline powder |
|
Solubility |
Practically insoluble in water; slightly soluble in ethanol; soluble in dimethyl sulfoxide |
|
Storage Conditions |
Store in a tightly closed container, protected from light and moisture, at 2°C to 8°C |
|
Shelf Life |
24 months (re-test period based on stability data) |
Quality & Analytical Standards
|
Quality Attribute |
Acceptance Criteria |
Test Method |
|
Assay (Anhydrous Basis) |
99.0% – 101.0% |
High-Performance Liquid Chromatography |
|
Appearance of Solution |
Clear and colorless (0.5g in 25mL DMSO) |
Visual Inspection |
|
Water Content |
Maximum 0.5% |
Volumetric Titration |
|
Residue on Ignition |
Maximum 0.1% |
Gravimetric Analysis |
|
Heavy Metals |
Maximum 10 ppm |
Inductively Coupled Plasma Mass Spectrometry |
|
Individual Specified Impurity |
Maximum 0.10% |
High-Performance Liquid Chromatography |
|
Total Impurities |
Maximum 0.50% |
High-Performance Liquid Chromatography |
|
Residual Solvents |
Compliant with ICH Q3C limits |
Gas Chromatography |
|
Particle Size Distribution (D90) |
Maximum 50 µm (Micronized grade available) |
Laser Diffraction |
Manufacturing & Supply Chain Standards
Production Route: Multi-step convergent synthesis utilizing chiral resolution and palladium-catalyzed coupling reactions.
Batch Scale: Pilot scale to multi-kilogram commercial production.
Containment Level: OEB 4 reactor suites equipped with closed-system isolators.
Facility Classification: Grade D synthesis isolation paired with Grade C micronization and packaging suites.
In-Process Controls: Real-time reaction monitoring via high-performance liquid chromatography, gas chromatography-mass spectrometry, and automated temperature-pressure logging.
Regulatory Documentation Support
- Comprehensive Drug Master File compiled in ICH CTD format available for reference authorization.
- Certificate of Analysis provided for every manufactured batch.
- Certificate of Suitability supporting data packages.
- Comprehensive impurity profile reports including genotoxic impurity assessments based on ICH M7 guidelines.
- Analytical validation packages including method transfer protocols for assay, residual solvents, and particle size distribution.
- Safety Data Sheet detailing handling, storage, and toxicological thresholds.
Packaging & Storage Specifications
|
Primary Packaging |
Double-layer pharmaceutical-grade low-density polyethylene bags, heat-sealed under a continuous nitrogen purge. |
|
Secondary Packaging |
Rigid fiber drums or aluminum-laminated barrier containers equipped with tamper-evident seals. |
|
Desiccant Integration |
Pharmaceutical-grade silica gel packets placed between primary and secondary layers for moisture barrier protection. |
|
Standard Pack Sizes |
1 kg, 5 kg, and 25 kg net weight per drum. |
Pharmaceutical Applications
Rheumatoid Arthritis Therapy: Functions as a Janus kinase inhibitor targeting intracellular cytokine signaling cascades to reduce joint inflammation, cartilage degradation, and structural joint damage in moderate-to-severe autoimmune conditions. Formulated as the active core in oral film-coated tablets designed for once-daily chronic therapeutic regimens.
Alopecia Areata Treatment: Blocks immune-mediated pathways attacking hair follicles by selectively suppressing inflammatory cytokine signaling in dermatological tissue layers. Formulated into solid oral dosage presentations to restore hair growth in severe autoimmune scalp conditions.
Systemic Inflammatory Management: Modulates aberrant immune responses by interrupting signal transduction pathways driven by interleukins and interferons. Utilized in specialized clinical trial formulations and targeted therapeutic delivery systems.
FAQ
Q: What is the current regulatory status and DMF availability?
A: A comprehensive Drug Master File has been compiled in accordance with ICH CTD format requirements and is accessible for reference authorization upon signing a Letter of Access.
Q: How are critical impurities controlled during synthesis?
A: Impurities are monitored across all synthetic steps using validated analytical methods, ensuring levels remain strictly below established ICH threshold limits.
Q: What temperature controls are required during shipping?
A: The product must be stored at 2°C to 8°C. Validated thermal shipping containers equipped with continuous data loggers are utilized to maintain specified temperature ranges throughout transit.
Q: Can the particle size distribution be customized?
A: Yes, micronization parameters can be adjusted during secondary processing to achieve specific D90 targets matching client formulation and dissolution profiles.
Q: What is the standard sample quantity for evaluation?
A: Sample quantities for analytical evaluation start at 100 grams, while commercial batch orders are established based on multi-batch annual forecast agreements.
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