Carvedilol is a non-selective beta-adrenergic and selective alpha-1 adrenergic blocking agent utilized in oral formulations for hypertension, chronic heart failure, and left ventricular dysfunction post-myocardial infarction. Manufactured as a white to off-white crystalline powder, it reduces vascular resistance and suppresses the renin-angiotensin-aldosterone system. Precise control over crystal polymorphism and particle size distribution ensures optimal dissolution kinetics and bioavailability in finished solid dosage forms.
Technical Specifications
|
Parameter |
Technical Specification |
|
INN |
Carvedilol |
|
Chemical Name |
1-(9H-carbazol-4-yloxy)-3-[[2-(2-methoxyphenoxy)ethyl]amino]propan-2-ol |
|
CAS Registry Number |
72956-09-3 |
|
Physical Description |
White to off-white powder |
|
Solubility |
Practically insoluble in water; sparingly soluble in methanol and ethanol; soluble in dimethyl sulfoxide |
|
Melting Range |
114°C to 117°C |
|
Storage Conditions |
Store in tightly closed containers protected from light and moisture at controlled room temperature |
|
Shelf Life |
36 months from manufacturing date |
Quality & Analytical Compliance
Assay (Calculated on dried basis): 98.0% to 102.0% (Ph.Eur. / USP Compliance)
Appearance of Solution: Clear and practically colorless in methanol
Loss on Drying: Maximum 0.5%
Residue on Ignition / Sulfated Ash: Maximum 0.1%
Heavy Metals: Maximum 10 ppm
Individual Specified Impurity: Maximum 0.10%
Total Impurities: Maximum 0.5%
Residual Solvents (GC): Methanol maximum 3000 ppm, Ethanol maximum 5000 ppm, Toluene maximum 890 ppm
Particle Size Distribution (D90): Custom milling options available for D90 below 10 micrometers or 50 micrometers
Microbial Limits: Total aerobic microbial count maximum 1000 CFU per gram; total yeast and mold maximum 100 CFU per gram; absence of Escherichia coli and Salmonella
Manufacturing Standards
Synthesis Route: Multi-step organic synthesis utilizing controlled condensation and chiral resolution steps
Batch Scale: Commercial scale production ranging from 200 kg to 500 kg per batch
Cleanroom Classification: ISO Class 8 areas for final isolation, drying, and micronization
Containment: Closed-system reactors and automated filtration units to prevent cross-contamination
In-Process Controls: High-performance liquid chromatography purity checks, residual solvent monitoring, and moisture titration at critical reaction endpoints
Supply Capacity: Regular annual tonnage allocation with established safety stock management
Regulatory Documentation
Drug Master File (DMF): Open-part DMF available for regulatory submission
Certificate of Analysis (CoA): Provided with every commercial and sample shipment
Certificate of Suitability (CEP): Available upon formal request and project evaluation
Safety Data Sheet (SDS): Compliant with global chemical safety regulations
GMP Compliance Statement: Issued by national regulatory authorities
TSE/BSE Statement: Certified free from animal-derived raw materials
Genotoxic Impurity Evaluation Data: Comprehensive risk assessment package available
Packaging & Chain of Custody
Food-grade double low-density polyethylene bags, heat-sealed under nitrogen purge
Fiber drums or rigid UN-approved cardboard drums
25 kg per drum with custom packaging configurations available upon request
Serialized security seals applied to all drum closures to ensure chain of custody integrity
Pharmaceutical Applications
Immediate-Release Tablet Formulations: Compressed into oral tablets ranging from 3.125 mg to 25 mg for chronic hypertension management, requiring tight particle size control for uniform dissolution profiles.
Extended-Release Capsule Formulations: Incorporated into multi-particulate pellet systems for once-daily extended-release capsule configurations, demanding strict bulk density consistency and low impurity profiles.
Combination Therapy Formulations: Utilized in co-formulated solid dosage presentations combining beta-blockade mechanisms with diuretic agents, requiring high chemical stability and compatibility with standard excipients like lactose monohydrate and microcrystalline cellulose.
Post-Myocardial Infarction Recovery Regimens: Processed into specialized low-dose tablets deployed in post-infarct clinical protocols, necessitating rigorous batch-to-batch enantiomeric purity and strict control over degradation products.
FAQ
Q: What is the standard batch size and minimum order quantity for commercial orders?
A: Commercial production batches are manufactured at standard scale, with minimum order quantities established during contract negotiation to align with stability testing and regulatory filing requirements.
Q: Is an open-part Drug Master File accessible for regulatory review?
A: Yes, a comprehensive Drug Master File is maintained and available for referencing in support of abbreviated new drug applications or marketing authorizations in regulated jurisdictions.
Q: What specific particle size distribution profiles can be supplied?
A: The material can be processed via specialized air-jet milling to achieve tailored particle size distribution ranges, such as D90 below 10 micrometers, to accommodate specific dissolution requirements for solid dosage formulation.
Q: How are moisture-sensitive and light-sensitive properties managed during transit?
A: Packaging utilizes double-layer polyethylene bags sealed under nitrogen within rigid light-impermeable drums, preventing degradation induced by ambient humidity or ultraviolet exposure during global freight transport.
Q: What analytical methods are provided for quality control verification?
A: A complete analytical testing validation package-including high-performance liquid chromatography assay methods, impurity separation parameters, and residual solvent quantification procedures-is supplied upon technical transfer request.
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