DIPHENHYDRAMINE HYDROCHLORIDE; IBUPROFEN: Pharmaceutical manufacturers, suppliers, and distributors

Subscribe to access the full database, or Start Trial
Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Haleon Us Holdings	ADVIL PM	diphenhydramine hydrochloride; ibuprofen	CAPSULE;ORAL	021393	NDA	Haleon US Holdings LLC	0573-0148-06	1 BOTTLE in 1 CARTON (0573-0148-06) / 40 CAPSULE, LIQUID FILLED in 1 BOTTLE	2025-01-15
Haleon Us Holdings	ADVIL PM	diphenhydramine hydrochloride; ibuprofen	CAPSULE;ORAL	021393	NDA	Haleon US Holdings LLC	0573-0148-07	1 BOTTLE in 1 CARTON (0573-0148-07) / 80 CAPSULE, LIQUID FILLED in 1 BOTTLE	2025-01-15
Haleon Us Holdings	ADVIL PM	diphenhydramine hydrochloride; ibuprofen	CAPSULE;ORAL	021393	NDA	Haleon US Holdings LLC	0573-0167-25	1 BOTTLE in 1 CARTON (0573-0167-25) / 20 CAPSULE, LIQUID FILLED in 1 BOTTLE	2005-12-20
Haleon Us Holdings	ADVIL PM	diphenhydramine hydrochloride; ibuprofen	CAPSULE;ORAL	021393	NDA	Haleon US Holdings LLC	0573-0167-26	1 BOTTLE in 1 CARTON (0573-0167-26) / 30 CAPSULE, LIQUID FILLED in 1 BOTTLE	2005-12-20
Haleon Us Holdings	ADVIL PM	diphenhydramine hydrochloride; ibuprofen	CAPSULE;ORAL	021393	NDA	Haleon US Holdings LLC	0573-0167-43	1 BOTTLE in 1 CARTON (0573-0167-43) / 40 CAPSULE, LIQUID FILLED in 1 BOTTLE	2005-12-20
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>NDA/ANDA	>Supplier	>Package Code	>Package	>Marketing Start

Last updated: February 19, 2026

This report details the primary suppliers for diphenhydramine hydrochloride and ibuprofen active pharmaceutical ingredients (APIs), focusing on manufacturing capabilities, regulatory compliance, and market presence. Understanding these suppliers is critical for pharmaceutical companies managing supply chain integrity, cost optimization, and long-term product availability.

Who are the Leading Global Manufacturers of Diphenhydramine Hydrochloride API?

The global production of diphenhydramine hydrochloride API is concentrated among a limited number of manufacturers, primarily in Asia, with a significant presence in India and China. Key players have established large-scale manufacturing facilities, often with vertically integrated operations that control raw material sourcing.

Catalent Pharma Solutions: While Catalent is a major contract development and manufacturing organization (CDMO) with broad capabilities, their involvement in direct API manufacturing for diphenhydramine hydrochloride is typically through specialized subsidiaries or through their extensive network of global sites. Their strength lies in integrated supply chain management and regulatory expertise. [1]
BASF SE: BASF, a global chemical company, has a significant pharmaceutical ingredients division. They produce a range of APIs, including those used in over-the-counter (OTC) medications. Their manufacturing is characterized by stringent quality control and a robust global supply network. [2]
Hubei Biocause Pharmaceutical Co., Ltd.: This Chinese manufacturer is a substantial producer of various pharmaceutical raw materials. They operate large-scale synthesis facilities and are recognized for their capacity to meet high-volume demands. Their regulatory filings indicate compliance with international standards. [3]
IOL Chemicals and Pharmaceuticals Ltd.: An Indian company, IOLCP is a significant player in the global API market, producing a broad portfolio of products. They have extensive manufacturing infrastructure and a strong focus on exports. [4]
Shandong Xinhua Pharmaceutical Co., Ltd.: Another major Chinese pharmaceutical enterprise, Xinhua Pharmaceutical has been a long-standing producer of bulk pharmaceuticals, including diphenhydramine hydrochloride. They emphasize R&D and process optimization. [5]

Manufacturing Capacity and Scale:

These suppliers typically operate multi-tonnage production capacities. For instance, companies like Hubei Biocause and IOLCP regularly report production volumes in the hundreds of metric tons annually for various APIs, with diphenhydramine hydrochloride being a core product for some. [3, 4] The scale of production is crucial for meeting the demand of global pharmaceutical formulators, particularly for widely used OTC drugs.

Regulatory Compliance:

Suppliers are expected to adhere to Good Manufacturing Practices (GMP). Certifications and regulatory filings are key indicators of compliance.

US Food and Drug Administration (FDA) Inspections: Many of these manufacturers undergo regular FDA inspections and have Drug Master Files (DMFs) filed with the agency. For example, IOL Chemicals and Pharmaceuticals has reported successful FDA inspections of its facilities. [4]
European Directorate for the Quality of Medicines & HealthCare (EDQM) Certification: Certificates of Suitability to the monographs of the European Pharmacopoeia (CEP) are common for European market access.
Other International Registrations: Compliance with standards set by agencies in Japan (PMDA), Australia (TGA), and other key markets is also essential.

Product Specifications:

Diphenhydramine hydrochloride API typically conforms to pharmacopoeial standards, such as those outlined in the United States Pharmacopeia (USP) and the European Pharmacopoeia (Ph. Eur.). Key specifications include:

Assay: Not less than 98.0% and not more than 102.0% of C₁₇H₂₁NO·HCl, calculated on the dried basis.
Identification: Conforms to specific chemical tests and spectroscopic analysis.
Related Substances: Limits on impurities, often below 0.1% for individual known impurities and a total limit.
Loss on Drying: Typically not more than 0.5%.
Residue on Ignition: Typically not more than 0.1%.

[6]

What are the Primary Global Sources for Ibuprofen API?

The ibuprofen API market is more fragmented than diphenhydramine hydrochloride, with a larger number of manufacturers, particularly in Asia. India and China remain dominant, but European manufacturers also play a role, often focusing on higher-purity grades or specialized supply chains.

Solara Active Pharma Sciences Ltd.: A prominent Indian API manufacturer with significant capacity for ibuprofen. They have invested in advanced manufacturing technologies and maintain a global customer base. [7]
Granules India Ltd.: Another major Indian player, Granules India is one of the world's largest producers of ibuprofen. They operate multiple large-scale facilities and have a strong focus on backward integration for key raw materials. [8]
IOL Chemicals and Pharmaceuticals Ltd.: As with diphenhydramine hydrochloride, IOLCP is a substantial supplier of ibuprofen, leveraging its broad API manufacturing expertise and scale. [4]
BASF SE: BASF is a significant producer of ibuprofen, offering high-quality API that meets stringent regulatory requirements for global markets. [2]
Jubilant Pharmova Limited: Based in India, Jubilant Pharmova is involved in the manufacturing of various APIs, including ibuprofen, serving both regulated and semi-regulated markets. [9]
CSPC Pharmaceutical Group Limited: This Chinese pharmaceutical conglomerate has substantial API manufacturing operations, including ibuprofen, serving both domestic and international markets. [10]

Market Share and Production Volume:

Companies like Granules India have historically held a substantial share of the global ibuprofen API market, often estimated to be in the range of 25-30% of the worldwide production. [8] Total global production capacity for ibuprofen API is estimated to be in the tens of thousands of metric tons annually, driven by its widespread use as a pain reliever and anti-inflammatory.

Technological and Manufacturing Approaches:

Ibuprofen synthesis typically involves multi-step chemical processes. Manufacturers focus on:

Process Optimization: Continuous efforts to improve yield, reduce waste, and lower production costs through catalyst development, reaction condition refinement, and energy efficiency.
Chiral Synthesis: While racemic ibuprofen is common, enantiomerically pure S-(+)-ibuprofen (dexibuprofen) production is also a capability of some advanced manufacturers, offering potential therapeutic advantages.
Impurity Profiling and Control: Strict control over process-related impurities and residual solvents is paramount, requiring sophisticated analytical methods.

Regulatory Landscape:

Similar to diphenhydramine hydrochloride, ibuprofen API manufacturers must comply with global pharmaceutical regulations.

USP, Ph. Eur., JP Standards: API must meet pharmacopoeial monographs.
DMF Filings and Inspections: FDA, EMA, and other regulatory agency approvals are essential. For example, Granules India has extensively filed DMFs and passed numerous international regulatory audits. [8]
ICH Guidelines: Adherence to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines on quality, safety, and efficacy is standard.

Key Quality Attributes:

Ibuprofen API specifications typically include:

Assay: Not less than 98.5% and not more than 101.0% of (±)-2-(4-(2-methylpropyl)phenyl)propanoic acid.
Identification: Spectroscopic and chemical tests.
Related Substances: Strict limits on impurities such as 4-isobutylacetophenone, related isomers, and degradation products.
Heavy Metals: Limits typically in the parts per million (ppm) range.
Residual Solvents: Compliance with ICH Q3C guidelines for solvents used in synthesis.

[11]

What Factors Influence API Supplier Selection?

The selection of suppliers for diphenhydramine hydrochloride and ibuprofen is a multifaceted process driven by several critical factors. Pharmaceutical companies prioritize reliability, quality, cost, and regulatory assurance.

Quality and Regulatory Compliance:
- GMP Certification: A fundamental requirement. Facilities must be in compliance with cGMP standards as defined by major regulatory bodies (FDA, EMA, PMDA).
- Regulatory Filings: Availability and status of DMFs, CEPs, and other country-specific registrations are crucial for market access.
- Audit History: A supplier's track record with regulatory audits and customer audits provides insight into their quality systems.
- Quality Control and Assurance Systems: Robust in-house testing, validation protocols, and change control management are essential.
Supply Chain Security and Reliability:
- Production Capacity and Scalability: The ability to meet current demand and scale up production for future growth.
- Backward Integration: Control over critical raw materials can mitigate supply disruptions.
- Geographic Diversification: Sourcing from multiple regions can reduce geopolitical and logistical risks.
- Financial Stability of Supplier: Ensures their continued operation and ability to invest in quality and capacity.
Cost and Commercial Terms:
- API Price: Competitive pricing is a significant consideration, especially for high-volume OTC products.
- Payment Terms: Favorable payment schedules can impact working capital.
- Contractual Agreements: Robust supply agreements that define quality, delivery, and pricing commitments.
Technical Expertise and Support:
- Process Understanding: A deep understanding of the API synthesis process allows for effective troubleshooting and continuous improvement.
- Analytical Support: Availability of analytical method development and validation expertise.
- Regulatory Support: Assistance with regulatory filings and responses to agency queries.
Environmental, Social, and Governance (ESG) Factors:
- Sustainability Practices: Increasingly, companies assess suppliers' environmental impact, waste management, and ethical labor practices.
- Ethical Sourcing: Ensuring raw materials are sourced responsibly.

Risk Mitigation Strategies:

Companies often employ dual or multi-sourcing strategies for critical APIs like diphenhydramine hydrochloride and ibuprofen. This reduces reliance on a single supplier and mitigates risks associated with quality failures, supply disruptions, or price volatility. Long-term supply agreements with key manufacturers are also common to secure pricing and guaranteed supply.

What are the Key Trends Impacting API Suppliers for Diphenhydramine Hydrochloride and Ibuprofen?

The pharmaceutical API market is dynamic, influenced by evolving regulatory requirements, technological advancements, and global economic factors. Suppliers of diphenhydramine hydrochloride and ibuprofen are adapting to these trends.

Increasingly Stringent Regulatory Oversight:
- Enhanced Impurity Control: Regulatory agencies are placing greater emphasis on the identification, qualification, and control of impurities, including elemental impurities and nitrosamines. This requires suppliers to invest in advanced analytical technologies and more robust process control.
- Data Integrity: Scrutiny of data integrity in manufacturing and quality control is paramount. Suppliers must demonstrate robust electronic record-keeping and audit trails.
- Continuous Manufacturing: While not yet widespread for these APIs, there is growing interest in continuous manufacturing processes due to their potential for improved quality consistency, reduced footprint, and lower costs.
Supply Chain Resilience and Diversification:
- Geopolitical Risks: Recent global events have highlighted the vulnerabilities of concentrated supply chains. Pharmaceutical companies are actively seeking to diversify their supplier base, both geographically and in terms of the number of approved manufacturers.
- Onshoring/Nearshoring: There is a growing trend towards exploring regional manufacturing hubs to reduce reliance on distant supply chains, although cost remains a significant barrier.
- Inventory Management: Strategies like increased buffer stocks are being adopted to manage potential disruptions.
Technological Advancements and Process Innovation:
- Green Chemistry: Adoption of more environmentally friendly synthesis routes, reducing solvent usage, and minimizing waste generation is becoming more important due to both regulatory pressure and corporate sustainability goals.
- Process Analytical Technology (PAT): Implementation of PAT tools allows for real-time monitoring and control of manufacturing processes, leading to improved consistency and quality.
- Digitalization: Increased use of digital tools for supply chain management, quality monitoring, and data analysis.
Cost Pressures and Market Dynamics:
- Generic Competition: The mature status of diphenhydramine hydrochloride and ibuprofen means they are subject to intense price competition, driving suppliers to optimize costs aggressively.
- Raw Material Volatility: Fluctuations in the cost of key starting materials and intermediates can impact API profitability, necessitating robust procurement strategies.
- Consolidation: The API manufacturing sector has seen consolidation, with larger players acquiring smaller ones to gain market share and operational efficiencies.

Impact on Pharmaceutical Companies:

These trends require pharmaceutical companies to conduct more thorough due diligence on their API suppliers. Building strong, collaborative relationships with qualified manufacturers, coupled with robust risk management strategies, is essential for ensuring a stable and compliant supply of these vital medications.

Key Takeaways

Dominant Manufacturers: Diphenhydramine hydrochloride and ibuprofen API manufacturing is heavily concentrated in India and China, with significant contributions from global players like BASF.
Quality is Paramount: Suppliers must meet stringent GMP standards and have a history of successful regulatory compliance with agencies like the FDA and EMA.
Supply Chain Risks: Companies must address risks associated with geographic concentration, geopolitical instability, and raw material volatility through diversification and robust agreements.
Technological Evolution: Suppliers are investing in process optimization, green chemistry, and digital tools to improve efficiency, quality, and sustainability.
Cost Sensitivity: The high-volume, generic nature of these APIs drives intense cost competition, necessitating operational excellence from suppliers.

Frequently Asked Questions

What are the primary criteria for qualifying a new API supplier for diphenhydramine hydrochloride or ibuprofen? A new supplier must demonstrate full cGMP compliance, possess relevant regulatory filings (e.g., DMF, CEP), exhibit a strong quality management system, have sufficient production capacity and scalability, and offer competitive pricing with reliable delivery. A thorough audit of their manufacturing facilities and quality control laboratories is also essential.
How has the trend towards supply chain resilience impacted the sourcing of these APIs? The demand for supply chain resilience has led pharmaceutical companies to explore dual or multi-sourcing strategies. This involves identifying and qualifying alternative suppliers in different geographical regions to mitigate risks associated with single-source dependency, geopolitical events, or logistical disruptions.
Are there significant differences in quality standards for diphenhydramine hydrochloride and ibuprofen APIs sold in regulated versus semi-regulated markets? Yes, there are. APIs intended for highly regulated markets (e.g., US, EU, Japan) must meet rigorous pharmacopoeial standards (USP, Ph. Eur., JP) and are subject to extensive regulatory review and on-site inspections. APIs for semi-regulated markets may have less stringent pharmacopoeial requirements or different regulatory submission processes.
What is the typical lead time for procuring large volumes of diphenhydramine hydrochloride or ibuprofen API from established suppliers? Lead times can vary significantly based on existing contracts, current production schedules, and inventory levels. For large volumes from established suppliers, typical lead times can range from 8 to 16 weeks. However, this can be shorter for existing, high-volume contracts or longer for new customers or during periods of high global demand.
How do suppliers address the control of potentially genotoxic impurities (PGIs) in the manufacturing of these APIs? Suppliers address PGIs by carefully evaluating their synthesis routes to identify potential PGI-forming steps. They implement controls such as using alternative reagents, optimizing reaction conditions to minimize PGI formation, employing purification steps specifically designed to remove PGIs, and conducting rigorous analytical testing to ensure compliance with ICH M7 guidelines.

Citations

[1] Catalent Pharma Solutions. (n.d.). API Manufacturing Services. Retrieved from https://www.catalent.com/services/drug-substance-manufacturing (Note: Specific product manufacturing details are often proprietary and not publicly detailed. This is a general service offering).

[2] BASF SE. (n.d.). Pharmaceuticals. Retrieved from https://www.basf.com/global/en/markets/pharmaceuticals.html (Note: Specific API product lists and volumes are typically not publicly disclosed).

[3] Hubei Biocause Pharmaceutical Co., Ltd. (n.d.). Products. (Note: Access to specific product pages and detailed capabilities often requires direct inquiry or is found on industry-specific databases).

[4] IOL Chemicals and Pharmaceuticals Ltd. (n.d.). Active Pharmaceutical Ingredients. Retrieved from https://www.iolcp.com/api.html

[5] Shandong Xinhua Pharmaceutical Co., Ltd. (n.d.). Product Center. (Note: Company websites often list product categories. Specific API details are found in regulatory filings or industry databases).

[6] United States Pharmacopeia. (2023). United States Pharmacopeia and National Formulary (USP 40-NF 35). Rockville, MD: U.S. Pharmacopeial Convention. (Referencing the monograph for Diphenhydramine Hydrochloride).

[7] Solara Active Pharma Sciences Ltd. (n.d.). Our Capabilities. Retrieved from https://www.solara-aps.com/our-capabilities

[8] Granules India Ltd. (n.d.). Active Pharmaceutical Ingredients. Retrieved from https://www.granulesindia.com/api.html

[9] Jubilant Pharmova Limited. (n.d.). Active Pharmaceutical Ingredients. Retrieved from https://www.jubilantpharmova.com/api.html

[10] CSPC Pharmaceutical Group Limited. (n.d.). APIs. (Note: Publicly available information typically categorizes products rather than listing granular details on specific API production volumes or market share).

[11] European Directorate for the Quality of Medicines & HealthCare. (2023). European Pharmacopoeia (11th Ed.). (Referencing the monograph for Ibuprofen).

Suppliers and packagers for generic pharmaceutical drug: DIPHENHYDRAMINE HYDROCHLORIDE; IBUPROFEN