List of Excipients in Branded Drug IOHEXOL

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Generic Drugs Containing IOHEXOL

Company	Ingredient	NDC	Excipient
Amneal Pharmaceuticals Private Limited	iohexol	80830-2467	EDETATE CALCIUM DISODIUM
Amneal Pharmaceuticals Private Limited	iohexol	80830-2467	HYDROCHLORIC ACID
Amneal Pharmaceuticals Private Limited	iohexol	80830-2467	SODIUM HYDROXIDE
Amneal Pharmaceuticals Private Limited	iohexol	80830-2467	TROMETHAMINE
Amneal Pharmaceuticals Private Limited	iohexol	80830-2467	WATER

What are the Most Frequently-Used Excipients in IOHEXOL?

# Of NDCs	Excipient
1	EDETATE CALCIUM DISODIUM
1	HYDROCHLORIC ACID
1	SODIUM HYDROXIDE
1	TROMETHAMINE
1	WATER

Iohexol Excipient Strategy and Commercial Opportunities in Contrast Media

Last updated: September 5, 2026

Iohexol is an established, off-patent, nonionic iodinated contrast agent used for computed tomography, angiography, urography, and selected intrathecal procedures. The core commercial opportunity is not molecule ownership. It is differentiated parenteral formulation, manufacturing reliability, packaging, workflow integration, and supply resilience.

The reference product, Omnipaque, uses a relatively simple aqueous formulation built around iohexol, tromethamine, calcium disodium edetate, water for injection, and pH adjustment with hydrochloric acid or sodium hydroxide. Because the product is administered intravenously, intra-arterially, intrathecally, or orally depending on concentration and indication, excipient selection is constrained by sterility, osmolality, neurotoxicity, elemental impurities, container compatibility, and regulatory precedent.

What is iohexol and how is it marketed?

Iohexol is a water-soluble, nonionic, low-osmolar iodinated contrast medium. It is marketed primarily as an injectable solution under the Omnipaque brand and through generic or authorized-generic products.

Attribute	Iohexol
Active ingredient	Iohexol
Therapeutic class	Nonionic iodinated contrast agent
Main use	X-ray and CT contrast enhancement
Administration	Intravenous, intra-arterial, intrathecal, oral or body-cavity use depending on product and concentration
Common iodine strengths	140, 180, 240, 300 and 350 mg iodine/mL
Reference brand	Omnipaque
Original developer	Nycomed, later incorporated into GE Healthcare’s contrast-media business
Current commercial owner of Omnipaque in the U.S.	GE HealthCare
U.S. regulatory status	Approved prescription drug
Patent position	Core compound and original formulation protection are expired
Main competitive barriers	Sterile manufacturing, validated supply chain, regulatory compliance and hospital procurement access

Iohexol competes with iopamidol, ioversol, iopromide, iodixanol and older ionic agents. The choice is often determined by procedure, iodine concentration, viscosity, renal-risk protocols, hospital contracts and inventory availability rather than by a single clinical superiority claim.

What excipients are used in iohexol injection?

The commercial excipient system is intentionally limited. The U.S. Omnipaque labeling identifies tromethamine and calcium disodium edetate as formulation components, with hydrochloric acid or sodium hydroxide used for pH adjustment and water for injection as the vehicle (GE HealthCare, 2023).

Excipient or component	Primary formulation role	Commercial relevance
Water for injection	Sterile aqueous vehicle	Controls purity, endotoxin burden and injectable quality
Tromethamine	Buffering agent	Stabilizes pH during shelf life
Calcium disodium edetate	Chelating agent	Binds trace metals that can catalyze degradation or discoloration
Hydrochloric acid	pH adjustment	Supports target pH during manufacture
Sodium hydroxide	pH adjustment	Fine-tunes final pH
Nitrogen or controlled headspace, where used	Oxidation control	Packaging and stability strategy rather than an active excipient

The formulation does not rely on antimicrobial preservatives. That is important because iohexol is supplied for parenteral use in single-dose containers, and preservative-free presentation reduces concerns about preservative toxicity, intrathecal administration and compatibility with sensitive procedures.

Why is tromethamine used in iohexol?

Tromethamine, also known as tris or trometamol, provides buffering capacity. A stable pH supports product shelf life, limits degradation pathways and helps maintain compatibility with the container system.

The buffer must be controlled carefully. Excess buffer can affect osmolality and ionic composition, while insufficient buffer can permit pH drift during storage. A commercial developer should not assume that replacing tromethamine with phosphate, citrate or another buffer will be a simple substitution. Each alternative would require compatibility, stability, extractables and toxicology assessment.

Why is calcium disodium edetate used?

Calcium disodium edetate acts as a chelating agent. It can reduce the impact of trace metal contamination on chemical stability. Its use also reflects the sensitivity of high-concentration aqueous contrast formulations to raw-material quality, equipment surfaces and container components.

Chelator concentration is a development variable with a narrow practical range. Too little may not control metal-catalyzed degradation. Too much can complicate impurity qualification, analytical control and regulatory justification.

What formulation characteristics define iohexol commercial performance?

Iohexol products are differentiated less by novel excipients than by the interaction between iodine concentration, viscosity, osmolality, pH, sterility and delivery format.

Formulation variable	Commercial effect
Iodine concentration	Determines image quality, injection volume and procedure suitability
Viscosity	Affects injection pressure, flow rate and catheter performance
Osmolality	Influences tolerability and fluid shifts
pH	Supports stability and injection compatibility
Fill volume	Determines use in CT injectors, angiography and multidose workflow
Container format	Affects preparation time, waste and pharmacy handling
Sterilization method	Affects degradation, particulate control and packaging choice
Storage conditions	Affect hospital inventory and global distribution

Higher iodine concentrations can reduce the volume needed for a target iodine dose, but they can also increase viscosity. Hospitals may therefore value concentration-specific products rather than one universal formulation.

What excipient strategy is most attractive for new iohexol products?

The strongest strategy is usually a low-change, regulatory-conservative formulation supported by manufacturing and packaging improvements.

Strategy 1: Preserve the reference excipient system

A formulation that matches the established excipient architecture can reduce development risk. This approach supports comparative analytical studies, pharmaceutical equivalence arguments and possible abbreviated regulatory pathways where applicable.

The drawback is limited differentiation. A reference-like product will compete mainly on price, supply continuity, customer service and contract terms.

Strategy 2: Develop a lower-viscosity presentation

A lower-viscosity product could target high-flow CT and angiography workflows. Potential approaches include concentration-specific viscosity optimization, tighter control of iohexol distribution and improved temperature-management instructions.

This opportunity is technically difficult. Viscosity depends heavily on iodine concentration and temperature. A product that performs well at room temperature may behave differently in cold storage or during emergency use. Any claim relating to faster injection or lower injector pressure requires procedure-specific validation.

Strategy 3: Offer optimized ready-to-use packaging

Commercial value can come from containers rather than new chemistry. Opportunities include:

• Preconnected syringe systems for CT injectors
• Small-volume presentations for pediatric or low-dose workflows
• Large-volume bags for high-throughput imaging departments
• Reduced-overfill containers
• Latex-free and low-extractables packaging
• Unit-dose formats that reduce manipulation and waste
• Barcoded containers compatible with medication-management systems

The excipient system may remain unchanged while the product gains value through reduced preparation time, fewer transfer steps and better inventory control.

Strategy 4: Improve cold-chain and temperature robustness

Iohexol is generally stored under controlled room-temperature conditions according to product labeling, but distribution interruptions, temperature excursions and international shipping remain practical risks. A formulation and package system with stronger excursion stability could support emerging-market distribution and hospital stockpiling.

The commercial claim must be based on validated stability data. Packaging, headspace, container closure and transit qualification can matter as much as the excipient composition.

Strategy 5: Develop a preservative-free, intrathecal-focused presentation

Preservative-free presentation is already important for intrathecal use. A product designed specifically for neuroradiology could differentiate through small fill volumes, clear labeling, low dead volume and procedure-specific packaging.

The clinical and regulatory burden is high. Intrathecal administration requires strict control of particulate matter, endotoxins, sterility, osmolality and neurotoxicity. Excipients with acceptable intravenous histories may require additional justification for intrathecal use.

What formulation patents protect iohexol products?

The original composition and manufacturing patents for iohexol are expired or no longer commercially meaningful in the United States and major developed markets. The core active ingredient is therefore exposed to generic competition.

Current protection is more likely to arise from:

• Device patents covering injector systems
• Container-closure and packaging patents
• Manufacturing process patents
• Concentration-specific handling systems
• Digital workflow and inventory technologies
• Combination claims involving contrast delivery equipment
• Trade secrets covering purification, impurity control and batch-release methods

An excipient combination that merely reproduces the established iohexol formulation is unlikely to create a strong standalone patent position unless it produces a measurable, unexpected technical result. Stronger patent candidates would involve a defined impurity profile, improved stability under a specific stress condition, reduced particulate formation, a validated low-viscosity profile or a novel container interaction.

What is the FDA regulatory status of iohexol?

Iohexol is an FDA-approved prescription contrast agent. Omnipaque labeling covers multiple concentrations and routes of administration, including intravascular and intrathecal uses for specified diagnostic procedures (FDA, 2023).

The regulatory pathway for a new generic iohexol injection is generally based on demonstrating pharmaceutical equivalence, bioequivalence or an appropriate alternative where systemic bioavailability studies are not suitable, and compliance with injectable-product quality requirements. The product must also satisfy requirements for sterility, endotoxins, particulate matter, impurities, container closure and stability.

A reformulated product with new excipients may not fit a simple generic strategy. A new excipient, a materially different concentration or an expanded indication can increase the need for additional toxicology, clinical bridging or a different regulatory submission.

What is the Orange Book status of iohexol?

Iohexol is an old small-molecule product with expired core exclusivity. The commercial question is not whether a basic iohexol formulation remains protected. It is whether a specific marketed product has current listed patents or regulatory exclusivity that could delay an abbreviated generic approval.

Orange Book review should be performed at the specific NDA and strength level because listed patents, supplements and product presentations can differ. In practice, the principal barriers for iohexol entrants are manufacturing validation, FDA review, injectable quality systems and customer access rather than active compound patents.

A Paragraph IV challenge would have limited value against expired core patents. It could still matter if a sponsor identifies an unexpired patent covering a particular formulation, device, method of use or presentation. The commercial effect would depend on the scope of the patent and whether the reference product remains within the relevant claims.

When does iohexol lose exclusivity?

Iohexol’s original market exclusivity and compound-level patent protection have already expired. The active ingredient is commercially genericized.

The practical timeline for a new entrant is therefore driven by regulatory and operational milestones:

Stage	Typical commercial significance
API qualification	Establishes impurity, residual-solvent and elemental-impurity controls
Formulation development	Confirms pH, viscosity, osmolality and stability
Container selection	Supports extractables, leachables and closure integrity
Process validation	Demonstrates sterile manufacturing capability
FDA submission	Creates review and inspection risk
Approval	Enables commercial launch, subject to supply readiness
Hospital contracting	Determines market penetration
Supply continuity	Often determines repeat purchasing

For a generic manufacturer, launch timing depends less on patent expiry than on approval status, manufacturing capacity and procurement contracts.

Which companies compete with iohexol?

Iohexol competes with branded and generic products from several contrast-media manufacturers.

Company	Relevant contrast-media products or position
GE HealthCare	Omnipaque and broader imaging contrast portfolio
Bracco	Iopamidol products, including Isovue
Bayer	Iopromide products, including Ultravist
Guerbet	Iobitridol and other contrast products in selected markets
Hologic and other specialty suppliers	Procedure-specific imaging products in selected channels
Generic manufacturers	Iohexol and competing nonionic iodinated contrast injections, depending on market

The competitive set differs by country. Local registration, hospital tenders, distributor networks and manufacturing location are often more important than global brand recognition.

What commercial opportunities exist for iohexol excipients?

The most attractive opportunities are adjacent to the drug rather than based on selling a commodity buffer or chelator.

Hospital efficiency

A ready-to-use product that reduces syringe preparation, vial transfer and waste can command procurement preference even without a new active ingredient. This is especially relevant in high-volume CT departments.

Supply-chain resilience

Iohexol supply has been vulnerable to manufacturing interruptions and concentrated global production. Regional filling, dual-source API qualification and strategically located sterile facilities can support premium contracts with hospital systems.

Pediatric and specialized imaging

Small-volume, clearly labeled, preservative-free presentations can target pediatric radiology, neuroradiology and outpatient imaging. The opportunity depends on packaging economics and clinical workflow fit.

Emerging markets

Demand is expanding with CT capacity, private imaging centers and hospital infrastructure. Products with stable room-temperature storage, simplified packaging and local regulatory support may compete effectively against imported brands.

Sustainable packaging

Reduced plastic use, recyclable secondary packaging and lower product overfill can improve procurement scores. Any packaging change must preserve container-closure integrity, sterility and chemical compatibility.

What manufacturing and intellectual-property barriers exist?

Iohexol is difficult to differentiate through conventional excipients because the formulation is mature and the excipient list is short. The stronger barriers are process and quality related.

Key barriers include:

• High-purity iohexol API supply
• Control of trace metals and degradation products
• Sterile compounding and aseptic filling
• High iodine-load solution handling
• Container extractables and leachables
• Particulate control
• Cold-temperature viscosity performance
• Large-scale terminal sterilization or validated aseptic processing
• Consistent fill volumes across multiple strengths
• Global pharmacopoeial compliance

Manufacturing know-how may be protected as trade secrets rather than patents. A competitor can reproduce the ingredient list but still fail to match impurity control, shelf life, particulate performance or batch consistency.

How strong is the iohexol patent estate?

The core patent estate is weak from a market-exclusivity perspective because iohexol is an established genericized active ingredient. A new entrant should not rely on compound patents to support premium pricing.

The strongest defensible positions are likely to be:

1. A validated formulation with superior stability or lower viscosity.
2. A proprietary container or injector interface.
3. A manufacturing process that improves yield or impurity control.
4. A procedure-specific presentation with workflow advantages.
5. A package and distribution system that reduces waste and temperature-excursion risk.

Patent strength should be assessed claim by claim. Broad claims covering common excipients such as tromethamine, edetate and water are unlikely to provide durable exclusivity unless tied to a narrow, unexpected technical effect.

What generic launch risks exist for iohexol?

Generic launch risk is moderate operationally and low from a core patent perspective.

The main risks are:

• Failure to demonstrate pharmaceutical equivalence
• Sterility or particulate deviations
• Inadequate stability at high iodine concentrations
• API shortages
• Limited sterile filling capacity
• Hospital preference for established suppliers
• Price compression after multiple entrants
• Product recalls affecting customer confidence
• Difficulties obtaining injector compatibility acceptance

A successful launch requires more than FDA approval. The manufacturer needs reliable supply, a broad concentration portfolio and a distribution model that fits radiology departments.

Key Takeaways

• Iohexol is an off-patent, genericized nonionic iodinated contrast agent.
• The established excipient system is simple: water for injection, tromethamine, calcium disodium edetate and pH adjusters.
• The strongest formulation opportunities involve viscosity, stability, packaging and workflow rather than new excipient claims.
• Preservative-free, intrathecal-compatible presentations remain important for specialized imaging.
• Ready-to-use syringes, optimized fill volumes and low-waste packaging can create commercial differentiation.
• FDA and Orange Book issues are secondary to sterile manufacturing, supply reliability and hospital contracting.
• Patent protection is more viable for devices, packaging, process controls and defined technical effects than for the basic iohexol formulation.
• The best commercial strategy is a reference-like formulation combined with differentiated delivery, regional supply and validated operational advantages.

FAQs About Iohexol Excipient Strategy

Is tromethamine safe for intravenous iohexol products?

Tromethamine is an established buffer in commercial iohexol injections. Its use is supported by product-specific regulatory precedent, but the concentration and final formulation must remain within validated quality and safety specifications.

Can phosphate replace tromethamine in iohexol injection?

A replacement may be technically possible, but it would require comparative stability, compatibility, osmolality, impurity and regulatory evaluation. Phosphate is not an automatic equivalent substitute.

Does iohexol contain preservatives?

Commercial parenteral iohexol products are generally formulated without antimicrobial preservatives. This is important for single-dose use and intrathecal administration.

Can a new iohexol formulation receive patent protection?

Yes, but a patent would need claims directed to a novel formulation, process, package, device or measurable technical result. The basic combination of iohexol, buffer, chelator and water is unlikely to support strong new exclusivity by itself.

Is iohexol a biosimilar opportunity?

No. Iohexol is a chemically synthesized small molecule, not a biologic. Competitive products are regulated as generic or follow-on drug products rather than biosimilars.

References

1. U.S. Food and Drug Administration. (2023). Omnipaque (iohexol injection) prescribing information.
2. GE HealthCare. (2023). Omnipaque: Iohexol injection prescribing information.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
4. U.S. Pharmacopeia. (2024). Iohexol monograph and general chapters for injectable drug products.
5. European Medicines Agency. (2023). Guideline on the sterilisation of the medicinal product, active substance, excipient and primary container.