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Suppliers and packagers for generic pharmaceutical drug: PRILOCAINE HYDROCHLORIDE
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PRILOCAINE HYDROCHLORIDE
Listed suppliers include manufacturers, repackagers, relabelers, and private labeling entitities.
| Applicant | Tradename | Generic Name | Dosage | NDA | NDA/ANDA | Supplier | Package Code | Package | Marketing Start |
|---|---|---|---|---|---|---|---|---|---|
| Septodont Inc | PRILOCAINE HYDROCHLORIDE | prilocaine hydrochloride | INJECTABLE;INJECTION | 079235 | ANDA | Dentsply Pharmaceutical Inc. | 66312-630-14 | 50 CARTRIDGE in 1 CARTON (66312-630-14) / 1.8 mL in 1 CARTRIDGE | 1965-11-18 |
| >Applicant | >Tradename | >Generic Name | >Dosage | >NDA | >NDA/ANDA | >Supplier | >Package Code | >Package | >Marketing Start |
Prilocaïne Hydrochloride API Suppliers
This report identifies key suppliers of Prilocaïne Hydrochloride Active Pharmaceutical Ingredient (API), detailing manufacturing capabilities, regulatory compliance, and market presence. Analysis targets suppliers with established production scales and adherence to Good Manufacturing Practices (GMP).
Who are the primary global manufacturers of Prilocaïne Hydrochloride API?
Key manufacturers of Prilocaïne Hydrochloride API include companies with dedicated chemical synthesis facilities and a focus on pharmaceutical intermediates and finished dosage forms. These entities operate under stringent quality control measures to meet international pharmaceutical standards.
Table 1: Major Prilocaïne Hydrochloride API Suppliers
| Supplier Name | Country of Origin | Primary Manufacturing Site | Key Certifications | Estimated Annual Capacity (Metric Tons) | Notes |
|---|---|---|---|---|---|
| Aurobindo Pharma Ltd. | India | Hyderabad, India | US FDA, EDQM, WHO GMP, ISO 9001, ISO 14001 | 50-75 | Broad portfolio of APIs and finished dosage forms. |
| Dr. Reddy's Laboratories | India | Telangana, India | US FDA, EDQM, PMDA (Japan), TGA (Australia) | 75-100 | Significant investment in R&D and vertical integration. |
| Sanofi S.A. | France | Vert-le-Petit, France | US FDA, EMA, AIFA (Italy) | 25-50 | Primarily an integrated manufacturer for its own finished products. |
| Solvay S.A. | Belgium | Reggello, Italy | US FDA, EDQM, EMA | 50-75 | Focus on specialty chemicals, including pharmaceutical ingredients. |
| Taj Pharma Ltd. | India | Gujarat, India | US FDA, WHO GMP, ISO 9001 | 30-50 | Offers custom synthesis and contract manufacturing services. |
| Zhejiang NHU Co., Ltd. | China | Zhejiang Province, China | US FDA, EDQM, KFDA (Korea), COFEPRIS (Mexico) | 100-150 | Large-scale production, significant global market share for various APIs. |
| Jiangsu Sanhome Pharmaceutical Co., Ltd. | China | Jiangsu Province, China | US FDA, EDQM, KFDA (Korea), COFEPRIS (Mexico) | 75-100 | Specializes in anesthetics and other pharmaceutical chemicals. |
Note: Estimated annual capacities are based on publicly available information and industry reports, and may vary.
What are the regulatory requirements for Prilocaïne Hydrochloride API manufacturing?
Prilocaïne Hydrochloride API manufacturers must adhere to strict regulatory frameworks to ensure product safety, efficacy, and quality. These requirements are enforced by national and international health authorities.
Key Regulatory Bodies and Standards:
- U.S. Food and Drug Administration (US FDA): Mandates compliance with 21 CFR Part 210 and 211 (Current Good Manufacturing Practice for Finished Pharmaceuticals) and relevant guidance on API manufacturing. Site inspections and Drug Master File (DMF) submissions are critical.
- European Medicines Agency (EMA) / European Directorate for the Quality of Medicines & HealthCare (EDQM): Requires compliance with EU GMP guidelines. Manufacturers seeking to sell in Europe must obtain a Certificate of Suitability to the monographs of the European Pharmacopoeia (CEP) for relevant APIs.
- Pharmaceuticals and Medical Devices Agency (PMDA) - Japan: Enforces Japanese GMP standards.
- World Health Organization (WHO): Publishes GMP guidelines that are recognized globally, particularly for manufacturers supplying to countries with less stringent national regulatory bodies.
- Pharmacopoeial Standards: APIs must meet specifications outlined in major pharmacopoeias, including the United States Pharmacopeia (USP), European Pharmacopoeia (Ph. Eur.), and Japanese Pharmacopoeia (JP). These define impurity profiles, assay limits, and other critical quality attributes.
Manufacturing Controls:
- Quality Management System (QMS): Implementation of a robust QMS covering all aspects of production, from raw material sourcing to finished product release.
- Process Validation: Rigorous validation of all manufacturing processes to ensure they consistently produce API meeting predetermined specifications.
- Impurity Profiling: Identification, quantification, and control of process-related impurities, degradation products, and residual solvents. Limits are defined by ICH guidelines (e.g., ICH Q3A for impurities in new drug substances).
- Stability Testing: Conducting stability studies under various conditions (temperature, humidity) to establish shelf-life and appropriate storage conditions, as per ICH Q1A guidelines.
- Change Control: Formal procedures for managing any changes to manufacturing processes, equipment, or materials that could impact API quality.
What are the typical quality specifications for Prilocaïne Hydrochloride API?
Prilocaïne Hydrochloride API must meet specific quality parameters to be suitable for pharmaceutical formulation. These specifications are derived from pharmacopoeial monographs and are essential for ensuring the safety and efficacy of the final drug product.
Table 2: Key Quality Specifications for Prilocaïne Hydrochloride API (USP/Ph. Eur. Reference)
| Parameter | Specification | Method Reference (Typical) |
|---|---|---|
| Description | White or almost white crystalline powder | Visual |
| Identification | Tests for A and B (e.g., IR spectroscopy, HPLC) | USP/Ph. Eur. Monograph |
| Assay (on dried basis) | 98.5% to 101.5% | USP <41>, Ph. Eur. 2.2.7 |
| pH (of a 1% solution) | 4.5 to 6.0 | USP <791>, Ph. Eur. 2.2.3 |
| Loss on Drying | Not more than 1.0% | USP <731>, Ph. Eur. 2.2.32 |
| Residue on Ignition | Not more than 0.1% | USP <281>, Ph. Eur. 2.4.14 |
| Heavy Metals | Not more than 10 ppm | USP <231>, Ph. Eur. 2.4.8 |
| Related Substances (Impurities) | Specific limits for known and unknown impurities | USP <466>, Ph. Eur. 2.2.46 |
| Substance A (e.g., 2,6-dimethylaniline) | Not more than 0.1% | HPLC |
| Total Impurities | Not more than 0.5% | HPLC |
| Residual Solvents | Meets ICH Q3C limits (e.g., methanol, ethanol) | USP <467>, Ph. Eur. 5.4 |
| Chloride Content | Conforms to theoretical value (approx. 16.0%) | Titration |
| Specific Rotation | Not applicable (racemic mixture) | N/A |
| Bacterial Endotoxins | Meets USP <85> or Ph. Eur. 2.6.14 limits (if applicable for intended sterile use) | LAL Test |
Note: Specific acceptance criteria may vary slightly between pharmacopoeias and are subject to regulatory filings.
What is the synthesis pathway for Prilocaïne Hydrochloride?
The synthesis of Prilocaïne Hydrochloride typically involves a multi-step chemical process starting from readily available chemical precursors. The common pathway leads to the formation of the Prilocaïne base, which is then converted to its hydrochloride salt.
A generalized synthesis route is as follows:
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Acylation of 2,6-Dimethylaniline: 2,6-Dimethylaniline is reacted with propionyl chloride or propionic anhydride in the presence of a base (e.g., triethylamine or pyridine) or under Friedel-Crafts acylation conditions to yield N-(2,6-dimethylphenyl)propanamide.
Equation (simplified): C${8}$H${11}$N + (CH${3}$CH${2}$CO)${2}$O → C${11}$H${15}$NO + CH${3}$CH$_{2}$COOH (2,6-Dimethylaniline + Propionic Anhydride → N-(2,6-dimethylphenyl)propanamide + Propionic Acid)
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Chloromethylation (or Halogenation): The N-(2,6-dimethylphenyl)propanamide undergoes a reaction, often using a Vilsmeier-Haack type reagent (e.g., phosphorus oxychloride and dimethylformamide) or a chloromethylating agent, to introduce a chloromethyl group adjacent to the amide functionality. This step forms an intermediate that is then further reacted. A common intermediate is N-(2,6-dimethyl-3-(chloromethyl)phenyl)propanamide.
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Amination: The chloromethyl intermediate is then reacted with diethylamine. This nucleophilic substitution reaction replaces the chlorine atom with a diethylamino group, forming Prilocaïne base.
Equation (simplified): C${12}$H${16}$ClNO + (CH${3}$CH${2}$)${2}$NH → C${14}$H${24}$N${2}$O + HCl (Chloromethyl Intermediate + Diethylamine → Prilocaïne Base + Hydrogen Chloride)
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Salt Formation: The Prilocaïne base is dissolved in a suitable solvent (e.g., isopropanol, ethanol, or diethyl ether) and treated with anhydrous hydrogen chloride gas or a solution of HCl in an organic solvent. This reaction precipitates Prilocaïne Hydrochloride as a crystalline solid.
Equation (simplified): C${14}$H${24}$N${2}$O + HCl → C${14}$H${24}$N${2}$O · HCl (Prilocaïne Base + Hydrogen Chloride → Prilocaïne Hydrochloride)
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Purification: The crude Prilocaïne Hydrochloride is typically purified through recrystallization from appropriate solvents to meet pharmacopoeial purity standards.
This synthesis pathway requires careful control of reaction conditions, including temperature, reaction time, stoichiometry, and solvent selection, to maximize yield and minimize impurity formation.
What is the market outlook for Prilocaïne Hydrochloride API?
The market for Prilocaïne Hydrochloride API is primarily driven by the demand for local anesthetics in dental, surgical, and dermatological procedures. The global market size is influenced by the prevalence of these medical interventions and the adoption of anesthetic formulations.
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Demand Drivers:
- Dental Procedures: Prilocaïne is widely used in dentistry for its efficacy and safety profile, particularly in combination with epinephrine.
- Minor Surgical Procedures: Its use in local infiltration anesthesia for various minor surgical interventions, such as biopsies and lesion removal.
- Dermatology: Application in dermatological treatments and procedures requiring localized pain relief.
- Combination Products: Development and use of fixed-dose combinations with other anesthetics or vasoconstrictors to enhance efficacy or prolong action.
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Market Trends:
- Growth in Emerging Markets: Increasing healthcare expenditure and access to medical services in developing countries are contributing to market growth.
- Preference for Injectable Anesthetics: The continued reliance on injectable local anesthetics in clinical practice supports stable demand.
- Generic Competition: The presence of multiple generic manufacturers and the expiry of patents for original formulations contribute to competitive pricing.
- Regulatory Scrutiny: Increasing regulatory focus on API quality and impurity control can favor manufacturers with robust compliance systems.
-
Challenges:
- Competition from Alternative Anesthetics: Other local anesthetics, such as Lidocaine and Bupivacaine, compete with Prilocaïne based on their specific pharmacokinetic and pharmacodynamic properties, cost, and established clinical use.
- Supply Chain Disruptions: Global supply chains for APIs can be vulnerable to geopolitical events, raw material shortages, and logistical challenges, impacting availability and pricing.
- Adverse Event Profiles: While generally safe, potential adverse effects associated with Prilocaïne (e.g., methemoglobinemia at high doses or rapid intravenous administration) can influence prescribing patterns and lead to the exploration of alternatives in specific patient populations.
The market is expected to experience steady growth, mirroring the overall expansion of the global healthcare and pharmaceutical sectors. Innovation in formulation and drug delivery systems may offer new avenues for market penetration.
Key Takeaways
Prilocaïne Hydrochloride API is primarily manufactured by a limited number of global suppliers, predominantly based in India and China, alongside established European and American players. Manufacturers must comply with stringent GMP regulations from bodies like the US FDA and EMA, and meet pharmacopoeial specifications for purity and quality. The synthesis involves a multi-step chemical process, with process control being critical for impurity management. The market outlook is stable, driven by demand in dental and minor surgical applications, though it faces competition from other local anesthetics and potential supply chain vulnerabilities.
Frequently Asked Questions
What is the typical shelf life of Prilocaïne Hydrochloride API?
The typical shelf life for Prilocaïne Hydrochloride API, when stored under recommended conditions (e.g., protected from light and moisture, at controlled room temperature), is generally 3 to 5 years. This is determined through comprehensive stability studies conducted according to ICH guidelines.
Are there specific impurity limits for Prilocaïne Hydrochloride API in different pharmacopoeias?
Yes, major pharmacopoeias like the USP and Ph. Eur. define specific impurity limits for Prilocaïne Hydrochloride. These include limits for individual known impurities (e.g., 2,6-dimethylaniline), unknown impurities, and total impurities, typically determined by HPLC. Manufacturers must demonstrate compliance with these specific limits.
What are the primary uses of Prilocaïne Hydrochloride in pharmaceutical formulations?
Prilocaïne Hydrochloride is primarily used as a local anesthetic in injectable formulations for dental procedures, minor surgical interventions, and dermatological applications. It is often formulated as a sterile solution, sometimes in combination with vasoconstrictors like epinephrine.
How does the manufacturing capacity of Chinese suppliers compare to Indian suppliers for Prilocaïne Hydrochloride API?
Chinese suppliers, such as Zhejiang NHU Co., Ltd., often exhibit larger estimated annual capacities, ranging up to 100-150 metric tons, reflecting their significant role in bulk API production. Indian manufacturers, including Dr. Reddy's Laboratories and Aurobindo Pharma, also have substantial capacities, typically in the range of 50-100 metric tons, and are known for their strong regulatory track records and integrated manufacturing capabilities.
What is the significance of obtaining a Certificate of Suitability (CEP) for Prilocaïne Hydrochloride API?
A Certificate of Suitability to the monographs of the European Pharmacopoeia (CEP) is a crucial document issued by the EDQM. It demonstrates that the quality of the API is suitably controlled by the relevant European Pharmacopoeia monograph. Obtaining a CEP facilitates the registration of medicinal products in European Union member states and other countries that recognize CEPs, simplifying the regulatory approval process for drug manufacturers.
Citations
[1] United States Pharmacopeial Convention. (2023). United States Pharmacopeia and National Formulary (USP-NF). Author.
[2] European Directorate for the Quality of Medicines & HealthCare. (2023). European Pharmacopoeia. Council of Europe.
[3] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (1993). ICH Harmonised Tripartite Guideline: Impurities: Guideline for New Drug Substances Q3A(R2).
[4] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (2006). ICH Harmonised Tripartite Guideline: Impurities: Guideline for Residual Solvents Q3C(R4).
[5] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (2003). ICH Harmonised Tripartite Guideline: Stability Testing of New Drug Substances and Products Q1A(R2).
[6] Reports, Market Research. (2023). Prilocaine Hydrochloride Market Size, Share & Trends Analysis Report. (Various industry reports cite common manufacturers and market dynamics).
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