Bulk Pharmaceutical API Sources for bendroflumethiazide

Bulk Pharmaceutical API Sources for bendroflumethiazide

Vendor	Vendor Homepage	Vendor Sku	API Url
NovoSeek		2315
MolPort		MolPort-003-666-443
NIH Clinical Collection		SAM002264598
ABI Chem		AC1L1DEI
ChemMol		49400511
TimTec		ST51014919

Bendroflumethiazide API Sourcing Landscape

Last updated: February 19, 2026

This report analyzes the global supply chain for bulk Bendroflumethiazide Active Pharmaceutical Ingredient (API). It identifies key manufacturers, production capacities, quality standards, and regulatory considerations impacting sourcing decisions for pharmaceutical companies. The analysis focuses on China and India as primary manufacturing hubs due to their established API production infrastructure and competitive pricing.

What are the primary global manufacturing centers for Bendroflumethiazide API?

The principal manufacturing centers for bulk Bendroflumethiazide API are located in China and India. These regions dominate global API production due to their established chemical manufacturing infrastructure, lower production costs, and skilled labor force.

• China: Possesses a significant number of API manufacturers, many of which are integrated with raw material suppliers. This integration can offer cost advantages and supply chain stability. Chinese manufacturers are known for large-scale production capabilities.
• India: A major exporter of pharmaceutical products and APIs, India has a well-developed regulatory framework and a strong focus on quality control. Indian API manufacturers often have extensive experience meeting international standards set by regulatory bodies like the US FDA and EMA.

While other countries may have niche producers, the bulk of global supply originates from these two nations.

Who are the key manufacturers of Bendroflumethiazide API?

Several manufacturers in China and India are prominent suppliers of Bendroflumethiazide API. Identification of specific manufacturers requires continuous market monitoring, as production capacities and market presence can shift. However, based on typical API supply chain structures and general knowledge of major pharmaceutical ingredient producers, the following categories of companies are likely involved:

• Large-scale chemical and pharmaceutical conglomerates: These companies often have diverse API portfolios and significant manufacturing footprints.
• Specialized API manufacturers: Companies focusing on a specific range of therapeutic classes, including diuretics, may be key suppliers.

Specific company names are subject to confidentiality agreements and dynamic market conditions. Pharmaceutical companies typically engage in direct sourcing, through distributors, or via tender processes to identify and secure suppliers. Due diligence, including site audits and quality agreement establishment, is critical.

What are the typical production capacities for Bendroflumethiazide API?

Production capacities for Bendroflumethiazide API vary significantly among manufacturers. Global demand dictates the scale of production. While exact figures are proprietary, manufacturers often operate in multi-tonnage annual capacities to achieve economies of scale.

• Small to Medium Manufacturers: May produce tens to hundreds of kilograms annually, serving regional markets or niche product lines.
• Large-scale Manufacturers: Can produce several metric tons of API per year. This scale is necessary to supply major generic drug manufacturers serving global markets.

Factors influencing capacity include:

• Reactor size and number
• Downstream processing capabilities (crystallization, drying, milling)
• Demand forecasts
• Regulatory compliance investments

What are the critical quality control and regulatory standards for Bendroflumethiazide API?

Ensuring the quality and regulatory compliance of Bendroflumethiazide API is paramount for patient safety and market access. Key standards include:

• Pharmacopoeial Standards: The API must comply with monographs in major pharmacopoeias:

  • United States Pharmacopeia (USP)
  • European Pharmacopoeia (Ph. Eur.)
  • British Pharmacopoeia (BP)
  • Japanese Pharmacopoeia (JP)

  These monographs specify purity, identification, assay, and impurity limits.

• Good Manufacturing Practices (GMP): Manufacturers must adhere to GMP guidelines established by regulatory authorities such as:

  • US Food and Drug Administration (FDA)
  • European Medicines Agency (EMA)
  • Pharmaceuticals and Medical Devices Agency (PMDA) of Japan
  • World Health Organization (WHO)

  GMP ensures consistent production and quality control.

• Drug Master Files (DMFs) / Active Substance Master Files (ASMFs): Manufacturers typically submit DMFs (in the US) or ASMFs (in Europe) to regulatory agencies. These confidential documents contain detailed information about the manufacturing process, quality controls, and facility. Pharmaceutical companies reference these filings in their drug product applications.

• Impurity Profiling: Rigorous testing for related substances and process impurities is required. Limits for known and unknown impurities are strictly defined by pharmacopoeias and regulatory guidelines (e.g., ICH Q3A).

• Stability Studies: API manufacturers must conduct comprehensive stability studies under various storage conditions (ICH Q1A) to establish shelf-life and re-test dates.

• Residual Solvents: Limits for residual solvents are governed by ICH Q3C guidelines. Manufacturers must demonstrate effective removal of solvents used in the synthesis.

• Heavy Metals and Other Contaminants: Testing for heavy metals and other potential contaminants is mandatory.

What are the typical analytical methods used for Bendroflumethiazide API quality assessment?

The quality assessment of Bendroflumethiazide API relies on a suite of validated analytical methods, ensuring it meets pharmacopoeial and regulatory requirements.

• Identification:

  • Infrared (IR) Spectroscopy: Compares the IR spectrum of the sample to a reference standard.
  • High-Performance Liquid Chromatography (HPLC): Retention time matching against a reference standard.
  • Ultraviolet (UV) Spectroscopy: Characteristic absorption maxima.

• Assay (Potency):

  • HPLC: This is the most common method, providing quantitative determination of Bendroflumethiazide content. Typical conditions involve reversed-phase chromatography with UV detection.
  • Titration: Acid-base titration may be used, though HPLC is generally preferred for its specificity and ability to detect impurities.

• Related Substances (Impurities):

  • HPLC: The primary technique for quantifying known and unknown impurities. Gradient elution is often employed to separate a wide range of related substances. Sensitivity is critical for detecting impurities at low levels (e.g., 0.05% or lower).
  • Gas Chromatography (GC): Used for the analysis of volatile impurities and residual solvents.

• Water Content:

  • Karl Fischer Titration: The standard method for determining water content.

• Residue on Ignition (Sulfated Ash):

  • Measures the amount of inorganic impurities remaining after ignition.

• Heavy Metals:

  • Often assessed using methods described in pharmacopoeias, which may involve colorimetric tests or instrumental techniques like Atomic Absorption Spectroscopy (AAS) or Inductively Coupled Plasma (ICP) spectroscopy.

• Particle Size Distribution:

  • Laser diffraction is commonly used to determine particle size distribution, which can impact dissolution rates and manufacturability of the finished dosage form.

• Polymorphism:

  • Techniques like X-ray Powder Diffraction (XRPD) and Differential Scanning Calorimetry (DSC) are used to identify and control the polymorphic form of the API, as different polymorphs can have varying solubility and stability.

What are the primary chemical synthesis routes for Bendroflumethiazide?

Bendroflumethiazide is a thiazide diuretic. Its synthesis typically involves multi-step chemical processes. While specific proprietary routes may exist, common synthetic strategies involve:

1. Formation of the Sulfonamide Core:

   • This often begins with the reaction of a substituted aniline with chlorosulfonic acid to form a sulfonyl chloride.
   • Subsequent amination with ammonia or an amine yields the sulfonamide.

2. Incorporation of the Trifluoromethyl Group:

   • The trifluoromethyl group (-CF3) is a key structural feature. Introducing this group can be achieved at various stages, often via fluorination reactions or by using trifluoromethyl-containing precursors. For example, 3-(trifluoromethyl)aniline is a common starting material.

3. Formation of the Thiazide Ring:

   • The thiazide ring system is typically constructed through cyclization reactions. A common approach involves reacting a suitably substituted o-amino benzenesulfonamide derivative with a reagent that introduces the two-carbon bridge and the nitrogen atom of the thiazide ring. This often involves condensation with reagents like formaldehyde and subsequent reactions.

A generalized synthetic pathway might involve:

• Starting with 3-(trifluoromethyl)aniline.
• Reacting it with chlorosulfonic acid to yield 4-amino-3-(trifluoromethyl)benzenesulfonyl chloride.
• Subsequent reaction with ammonia to form 4-amino-3-(trifluoromethyl)benzenesulfonamide.
• This intermediate then undergoes cyclization with appropriate reagents to form the benzothiadiazine-1,1-dioxide ring system, characteristic of thiazide diuretics.

The specific reagents, reaction conditions (temperature, pressure, solvents), catalysts, and purification steps are critical for achieving high yield and purity. Manufacturers continuously optimize these routes for cost-effectiveness, environmental impact, and adherence to quality standards.

What are the pricing trends and cost drivers for Bendroflumethiazide API?

Pricing for Bendroflumethiazide API is influenced by a combination of manufacturing costs, market demand, and competitive pressures.

Cost Drivers:

• Raw Material Costs: The price and availability of key chemical precursors, including trifluoromethyl-containing intermediates and reagents for sulfonation and amination, are primary drivers. Fluctuations in the petrochemical and specialty chemical markets directly impact these costs.
• Manufacturing Complexity and Yield: Multi-step synthesis processes with lower overall yields increase the cost per kilogram. Optimization of synthesis routes to improve yield and reduce waste is an ongoing effort.
• Regulatory Compliance: Investments in GMP-certified facilities, quality control laboratories, documentation, and personnel to meet stringent international standards add significant costs. Obtaining and maintaining DMF/ASMF filings also incurs substantial expenses.
• Energy and Labor Costs: These vary by manufacturing region. China and India generally offer lower energy and labor costs compared to Western countries, contributing to their competitive pricing.
• Environmental Regulations: Stricter environmental regulations can necessitate investments in wastewater treatment, emission control, and waste disposal, adding to manufacturing overhead.
• Scale of Production: Larger production volumes generally lead to lower per-unit costs due to economies of scale.
• Supply and Demand Dynamics: Market demand for Bendroflumethiazide, influenced by the prevalence of conditions treated by the drug and competition from alternative therapies, directly impacts pricing. Oversupply can lead to price erosion, while shortages can drive prices up.
• Geopolitical Factors and Trade Policies: Tariffs, trade disputes, and supply chain disruptions can affect the cost and availability of APIs.

Pricing Trends:

• Competitive Landscape: The market is characterized by a significant number of suppliers, particularly from China and India, leading to competitive pricing.
• Bulk vs. Smaller Quantities: Pricing is typically tiered, with significant discounts offered for larger bulk orders.
• Quality Premium: APIs that meet higher quality standards and have well-established regulatory filings (e.g., FDA-approved DMFs) may command a premium price.
• Long-term Contracts: Pharmaceutical companies often negotiate long-term supply agreements to secure stable pricing and supply.

Overall, the trend for Bendroflumethiazide API pricing has historically been driven by cost efficiencies in Asian manufacturing, tempered by increasing regulatory stringency and raw material price volatility.

What are the risks associated with sourcing Bendroflumethiazide API?

Sourcing bulk Bendroflumethiazide API involves several potential risks that pharmaceutical companies must proactively manage.

• Quality and Purity Risks:

  • Batch-to-batch variability: Inconsistent impurity profiles or potency across different manufacturing batches can lead to drug product quality issues and regulatory non-compliance.
  • Introduction of novel impurities: Process changes or deviations can lead to the formation of new, unidentified impurities that may be toxic or affect drug efficacy.
  • Counterfeit or sub-standard APIs: The global API market is susceptible to fraudulent products.

• Regulatory Risks:

  • Inspections and Warning Letters: Manufacturers may face regulatory inspections from agencies like the FDA or EMA. Findings of non-compliance can result in warning letters, import alerts, or the suspension of manufacturing activities, disrupting supply.
  • DMF/ASMF Deficiencies: Inadequate or outdated filings can delay or prevent the approval of drug product applications.
  • Evolving regulatory expectations: Changes in GMP guidelines, impurity control thresholds, or analytical requirements can necessitate costly updates to manufacturing processes and quality systems.

• Supply Chain and Geopolitical Risks:

  • Single-sourcing dependency: Relying on a single manufacturer or region creates vulnerability to production interruptions due to natural disasters, labor disputes, geopolitical instability, or unexpected facility shutdowns.
  • Logistical challenges: Transportation delays, customs issues, and increased freight costs can impact timely delivery.
  • Raw material shortages: Disruptions in the supply chain for critical starting materials or intermediates can halt API production.
  • Trade disputes and tariffs: Imposition of tariffs or trade barriers can increase the cost of imported APIs.

• Intellectual Property (IP) Risks:

  • While Bendroflumethiazide is an older drug with expired composition of matter patents, process patents or related IP could exist, requiring careful due diligence.

• Financial and Business Risks:

  • Manufacturer insolvency: The financial instability of a key supplier can lead to supply cessation.
  • Intellectual property disputes: While less common for established generics, the possibility of disputes over manufacturing processes exists.

• Environmental, Social, and Governance (ESG) Risks:

  • Increasing scrutiny on the environmental impact of chemical manufacturing and ethical labor practices can lead to reputational damage or supply disruptions if manufacturers fail to meet evolving ESG standards.

Mitigation strategies include dual/multi-sourcing, rigorous supplier qualification and auditing, robust quality agreements, proactive regulatory intelligence, and maintaining adequate safety stock.

Key Takeaways

1. Dominant Supply Hubs: China and India are the primary global sources for Bendroflumethiazide API, offering competitive pricing due to established infrastructure and cost efficiencies.
2. Quality is Paramount: Compliance with USP, Ph. Eur., and GMP standards, supported by robust DMF/ASMF filings, is critical for regulatory approval and market access.
3. Analytical Rigor: A comprehensive suite of analytical methods, including HPLC for assay and impurities, is essential for quality control.
4. Cost Drivers: Raw material prices, manufacturing complexity, regulatory compliance investments, and scale of production significantly influence API costs.
5. Risk Management: Pharmaceutical companies must address quality, regulatory, supply chain, and geopolitical risks through strategies like multi-sourcing and stringent supplier qualification.

Frequently Asked Questions

What is the typical lead time for ordering bulk Bendroflumethiazide API from Asian manufacturers?

Typical lead times for bulk Bendroflumethiazide API orders from manufacturers in China and India can range from 8 to 16 weeks. This duration accounts for manufacturing scheduling, production cycle time, quality control testing, documentation preparation, and shipment. Expedited production and shipping options may be available at a premium.

How can pharmaceutical companies verify the GMP compliance of a Bendroflumethiazide API manufacturer?

Verification of GMP compliance involves a multi-faceted approach. This includes reviewing the manufacturer's regulatory inspection history (e.g., FDA inspection reports, EMA EudraGMDP database), obtaining and scrutinizing their DMF/ASMF, conducting on-site audits of their manufacturing facilities and quality systems, and reviewing Certificates of Analysis (CoAs) for a representative number of batches.

Are there any significant differences in the quality of Bendroflumethiazide API produced in China versus India?

While both China and India produce high-quality APIs, there can be variations in specific impurity profiles or manufacturing process efficiencies between individual manufacturers. Historically, Indian manufacturers have been perceived as having a stronger, longer-standing track record with Western regulatory agencies. However, Chinese manufacturers have significantly advanced their quality systems and regulatory compliance. A thorough supplier qualification process is essential, irrespective of the country of origin, to ensure the chosen manufacturer meets all required quality and regulatory standards.

What are the common particle size specifications for Bendroflumethiazide API used in tablet formulations?

Particle size specifications for Bendroflumethiazide API used in tablet formulations are typically determined by the requirements of the specific drug product formulation and manufacturing process. Common specifications might include parameters like D10, D50 (median particle size), and D90, often measured by laser diffraction. For instance, a D50 value could range from 5 to 25 micrometers, and a D90 value from 20 to 70 micrometers, depending on the desired flowability, compressibility, and dissolution rate for the final dosage form.

What is the shelf life typically assigned to Bendroflumethiazide API, and under what storage conditions?

The typical shelf life assigned to Bendroflumethiazide API is usually 2 to 5 years, provided it is stored under controlled conditions. Recommended storage conditions generally involve keeping the API in well-closed containers, protected from light, at controlled room temperature (e.g., 20-25°C). Specific storage requirements are determined by detailed stability studies conducted by the manufacturer according to ICH guidelines and are clearly stated on the API's Certificate of Analysis and labeling.

Citations

[1] United States Pharmacopeial Convention. (2023). United States Pharmacopeia and The National Formulary (USP-NF). U.S. Pharmacopeia. [2] European Directorate for the Quality of Medicines & HealthCare. (n.d.). European Pharmacopoeia. EDQM. [3] Food and Drug Administration. (n.d.). Guidance Documents & Regulatory Information. FDA. [4] European Medicines Agency. (n.d.). European Medicines Agency Homepage. EMA. [5] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (n.d.). ICH Guidelines. ICH.