List of Excipients in Branded Drug OPTIRAY

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Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Liebel-Flarsheim Company LLC	OPTIRAY	ioversol	0019-1333	EDETATE CALCIUM DISODIUM
Liebel-Flarsheim Company LLC	OPTIRAY	ioversol	0019-1333	HYDROCHLORIC ACID
Liebel-Flarsheim Company LLC	OPTIRAY	ioversol	0019-1333	SODIUM HYDROXIDE
Liebel-Flarsheim Company LLC	OPTIRAY	ioversol	0019-1333	TROMETHAMINE

Optiray Excipient Strategy and Commercial Opportunities: Ioversol Formulation, Regulatory Status, and Market Outlook

Last updated: September 30, 2026

Optiray is an injectable iodinated contrast media product containing ioversol. Its excipient system is deliberately narrow: water for injection, tromethamine as a buffering agent, calcium disodium edetate as a chelating agent, and hydrochloric acid for pH adjustment. The strongest commercial opportunities are not conventional reformulation patents. They are supply-chain control, ready-to-use packaging, injector compatibility, storage performance, manufacturing reliability, and differentiated hospital-service models.

What is Optiray and which excipients does it contain?

Optiray is a nonionic, low-osmolar iodinated contrast agent for intravascular administration. It is used in radiographic procedures including computed tomography, angiography, intravenous digital subtraction angiography, and certain cardiac or visceral imaging procedures, depending on concentration and labeling.

The active pharmaceutical ingredient is ioversol. Optiray is sold in multiple iodine concentrations, including 240, 320, and 350 mg iodine/mL formulations in the United States.

Product attribute	Optiray profile
Active ingredient	Ioversol
Dosage form	Sterile aqueous injection
Administration	Primarily intravascular
U.S. concentrations	Optiray 240, Optiray 320, Optiray 350
Osmolality	Low-osmolar, concentration-dependent
Primary excipient	Water for injection
Buffer	Tromethamine
Chelating agent	Calcium disodium edetate
pH adjustment	Hydrochloric acid
Preservative	No conventional antimicrobial preservative identified in the U.S. labeling
Container strategy	Single-dose and procedure-oriented presentations, subject to current commercial configuration
Therapeutic class	Nonionic iodinated radiographic contrast agent

The U.S. prescribing information identifies tromethamine and calcium disodium edetate among the inactive ingredients. Hydrochloric acid is used for pH adjustment. The formulation does not rely on a complex surfactant, cosolvent, lipid system, polymer, or antimicrobial preservative architecture. That limits conventional excipient patent opportunities but reduces formulation complexity and supports manufacturing scale. (U.S. Food and Drug Administration, 2024a)

How does the Optiray excipient system work?

The excipients have functional, rather than therapeutic, roles.

Tromethamine provides pH control

Tromethamine, also known as tris(hydroxymethyl)aminomethane, buffers the solution. pH control helps maintain chemical stability, container compatibility, and tolerability during administration. The buffer system must operate without materially increasing osmolality or interacting with ioversol.

Commercially, buffer selection affects:

• Long-term pH drift
• Degradation-product formation
• Compatibility with glass and polymer containers
• Compatibility with automated injectors
• Tolerability at high injection rates
• Process robustness during terminal sterilization or aseptic filling

A competing product that changes the buffer would need to demonstrate that the new system does not alter impurity profiles, stability, viscosity, injectability, or clinical performance.

Calcium disodium edetate controls trace metals

Calcium disodium edetate is a chelating agent. It can bind trace metal ions that catalyze degradation reactions. The excipient is commercially important because trace-metal control is a low-concentration formulation variable with a direct effect on shelf life and batch consistency.

The main development risks are:

• Excessive chelation or interaction with container components
• Changes in impurity formation
• Assay and content-uniformity control at low concentration
• Compatibility with manufacturing equipment
• Regulatory justification for any substitute chelator

A replacement chelator could create an opportunity for a differentiated formulation, but it would also create a new quality-by-design burden. The commercial benefit must exceed the cost of new stability, extractables and leachables, toxicology, and regulatory work.

Hydrochloric acid adjusts final pH

Hydrochloric acid is used as a process and formulation adjustment component. It is not usually a meaningful standalone patent asset. Its commercial value lies in the manufacturing control strategy, including pH specification, order of addition, mixing sequence, and in-process testing.

Water for injection defines the bulk vehicle

Water for injection is the dominant vehicle. The formulation is therefore highly sensitive to:

• Bioburden and endotoxin control
• Bulk-water system qualification
• Filling-line performance
• Container closure integrity
• Sterility assurance
• Particulate control
• Storage and shipping conditions

The primary intellectual-property opportunity is more likely to arise from the manufacturing process and packaging configuration than from water as an excipient.

What formulations are protected by Optiray patents?

Optiray's commercial formulation is a mature, conventional aqueous ioversol formulation. No current commercial value should be assigned to broad composition-of-matter exclusivity for ioversol or to a basic excipient combination without a verified, enforceable patent claim.

The relevant protection categories are more likely to include:

Protection category	Potential relevance to Optiray	Commercial importance
Ioversol composition of matter	Low for current market protection	Low
Basic aqueous formulation	Limited for a mature product	Low to moderate
Buffer and chelator ratios	Possible if claim scope remains enforceable	Moderate
High-concentration stability	Potentially relevant	Moderate
Container closure system	Potentially relevant	Moderate
Injector-compatible packaging	Potentially relevant	Moderate to high
Manufacturing process	Potentially relevant	High if it reduces defects or improves yield
Premixed or ready-to-use presentation	Potentially relevant	High
Reduced-waste delivery system	Potentially relevant	Moderate to high
Method of use	Usually limited for a diagnostic contrast agent	Low to moderate

A patent strategy focused only on tromethamine, calcium disodium edetate, and water would face substantial written-description, enablement, obviousness, and freedom-to-operate risks. Stronger claims would connect the excipient system to a measurable technical result, such as improved stability at a specified iodine concentration, reduced particulate generation, lower extractables, or improved injector performance.

When does Optiray lose exclusivity?

Optiray is a small-molecule contrast agent, not a biologic. Biosimilar exclusivity rules do not apply. Generic competition proceeds through an abbreviated new drug application or another applicable small-molecule regulatory route, not through the biosimilar pathway.

The relevant commercial exclusivity has largely shifted from molecule-level protection to regulatory approval, manufacturing capability, supply reliability, and contracting position. FDA approval of a generic ioversol injection would not require the generic manufacturer to copy every commercial package configuration, but it would need to meet applicable quality, safety, efficacy, and labeling requirements.

Exclusivity issue	Optiray status
New chemical entity exclusivity	Historical issue; not a current commercial barrier for a mature ioversol product
Orphan-drug exclusivity	Not the relevant framework
Biologic reference-product exclusivity	Not applicable
Pediatric exclusivity	No current commercial significance identified
Patent-term extension	No current commercial significance identified
Orange Book patent blocking	Must be checked against the current FDA listing
Generic approval pathway	Small-molecule ANDA pathway is the principal route
Biosimilar challenge	Not applicable

What is the Orange Book status of Optiray?

Optiray's Orange Book relevance is narrower than that of a patented tablet or a biologic. The Orange Book identifies approved drug products and, where applicable, listed patents and exclusivity. A mature contrast agent with no blocking patent listing can face approval competition even while the branded product remains commercially active.

The business question is not whether Optiray has an FDA-approved NDA. It does. The question is whether any listed patent remains enforceable and capable of delaying an ANDA approval. That determination requires a current FDA Orange Book review, including the NDA number, patent-use codes, delisting activity, and any 30-month stay triggered by a Paragraph IV notice. (U.S. Food and Drug Administration, 2024b)

A patent search should cover:

1. Optiray 240, 320, and 350 product listings.
2. Ioversol injection ANDA approvals.
3. Patent numbers associated with formulation, manufacturing, or use.
4. Patent expiration and pediatric-extension dates.
5. Current and historical patent-use codes.
6. FDA correspondence concerning patent listing or delisting.
7. Court actions involving any Paragraph IV certification.

Which companies are challenging Optiray or competing with ioversol?

The competitive threat is broader than direct ioversol substitution. Hospitals and imaging networks purchase contrast media by clinical performance, price, supply security, injector compatibility, and vendor agreements.

Direct and adjacent competitors

Competitor or product family	Active ingredient	Competitive relationship
Generic ioversol injections	Ioversol	Direct substitution where approved and available
Omnipaque	Iohexol	Major competing nonionic iodinated contrast agent
Isovue	Iopamidol	Competing low-osmolar contrast agent
Visipaque	Iodixanol	Iso-osmolar alternative, often positioned for selected patients
Ultravist	Iopromide	Competing nonionic iodinated contrast agent
Iomeron	Iomeprol	International competitor, subject to jurisdictional approval
Optiray	Ioversol	Branded reference product

The direct generic threat depends on whether approved ioversol products are commercially available at scale. A nominal ANDA approval does not guarantee effective competition. Contrast media require sterile manufacturing, validated container systems, filling capacity, and dependable distribution. Manufacturing interruptions can leave a branded product with stronger pricing power than its patent position would suggest.

What Paragraph IV risks exist for Optiray?

A Paragraph IV certification is relevant only if an ANDA applicant identifies a listed patent and asserts that the patent is invalid, unenforceable, or not infringed. A Paragraph IV notice can trigger patent litigation and, under the Hatch-Waxman framework, a potential 30-month stay of approval.

For Optiray, the most plausible patent dispute targets would be:

• Concentration-specific stability claims
• Excipient-ratio claims
• Container or closure claims
• Sterilization and filling processes
• Injector-compatible packaging
• Method-of-use claims tied to a specific imaging protocol

A basic claim covering ioversol in water with routine buffer and chelator levels would face a higher vulnerability to obviousness challenges than a claim tied to an unexpected stability or compatibility result.

No current public litigation position should be inferred solely from the existence of an Optiray NDA. Litigation status must be tied to a specific patent number, ANDA filer, notice date, complaint, docket, and settlement term.

How strong is the Optiray patent estate?

The likely strength of the Optiray estate is moderate to weak at the broad formulation level and potentially stronger in narrow technical areas.

Estate component	Relative strength	Reason
Ioversol molecule	Low for current lifecycle defense	Mature small molecule
Broad aqueous formulation	Low	Predictable vehicle and excipient choices
Specific excipient ratios	Low to moderate	Strength depends on unexpected results
High-concentration stability	Moderate	May support narrower, defensible claims
Container closure and extractables	Moderate	Technical data can support non-obviousness
Injector delivery system	Moderate to high	Commercially relevant combination claims possible
Manufacturing controls	Moderate to high	Process know-how may be difficult to replicate
Hospital workflow integration	Moderate	More contractual than patent-based
Biosimilar barriers	Not applicable	Ioversol is not a biologic

Trade secrets may be more valuable than patents in this category. Bulk compounding order, filtration, mixing controls, trace-metal limits, filling parameters, particulate controls, and container-closure specifications can be difficult for a competitor to reproduce without access to the original development history.

What commercial opportunities exist in Optiray excipients?

The largest opportunities are lifecycle and supply-chain opportunities rather than new therapeutic claims.

1. Stabilized high-concentration formulations

A formulation that preserves ioversol stability at 320 or 350 mg iodine/mL while reducing impurity growth, viscosity, or particulate formation could support a differentiated product. Patent claims would need to identify a narrow excipient range and a measurable performance benefit.

2. Ready-to-use and injector-optimized packaging

Imaging centers value products that reduce preparation time and handling. Opportunities include:

• Preconnected syringe systems
• Larger-volume containers for high-throughput CT
• Small-volume presentations for selected procedures
• Compatibility with automated injectors
• Reduced dead volume
• Improved labeling and barcode integration
• Container designs that reduce residual waste

Packaging claims may be more commercially defensible than claims directed to routine excipient selection.

3. Polymer container development

Polymer containers can reduce breakage and handling weight but raise extractables, leachables, oxygen transmission, moisture transmission, and closure-integrity issues. A commercially valuable package would need to show acceptable stability across the product's shelf life and compatibility with high-pressure injection.

The IP opportunity could cover a container material, multilayer structure, closure, oxygen barrier, or filling process rather than the excipient system itself.

4. Lower-waste hospital delivery

Contrast media are administered in high-volume imaging environments. Products that reduce unused volume, simplify dose preparation, or improve inventory rotation may command value through hospital contracts even without a new composition patent.

5. Supply assurance and dual sourcing

Ioversol products require sterile manufacturing capacity and validated suppliers for primary packaging, excipients, and active ingredient. A second-source strategy for calcium disodium edetate, tromethamine, containers, and closures can reduce shortage exposure.

The commercial opportunity includes contract manufacturing, regional fill-finish, emergency inventory programs, and supply agreements with radiology networks.

6. Sustainable packaging

Reduced packaging weight, recyclable secondary materials, lower-volume shipping configurations, and improved container utilization can support tenders and health-system procurement. Environmental claims must be supported by validated lifecycle and disposal data.

What regulatory pathway applies to a new Optiray formulation?

A materially changed ioversol formulation would generally require an FDA submission that supports the proposed change. The pathway depends on whether the product is a pharmaceutical equivalent to an approved reference product and whether the change affects inactive ingredients, dosage form, strength, route, labeling, or manufacturing.

Key regulatory workstreams include:

• Comparative formulation characterization
• Pharmaceutical equivalence
• Sterility and endotoxin validation
• Particulate testing
• Extractables and leachables
• Container-closure integrity
• Accelerated and long-term stability
• High-pressure injector compatibility
• Osmolality, viscosity, pH, and iodine concentration
• In-use stability after container opening or device connection
• Labeling and adverse-event risk assessment

For an excipient substitution, the principal regulatory issue is not whether the excipient is generally recognized as safe in another context. It is whether the excipient is suitable at the proposed concentration, route, exposure, and product matrix.

What litigation and settlement agreements affect Optiray?

No litigation or settlement conclusion should be drawn without a docket-specific review. For a mature contrast agent, the relevant litigation categories are:

• Paragraph IV ANDA litigation
• Patent-listing disputes
• Manufacturing patent disputes
• Trade-secret litigation involving formulation or process know-how
• Contract disputes involving supply and distribution
• Product-liability litigation concerning hypersensitivity or administration events

Settlement agreements may include launch dates, licenses, authorized-generic rights, supply terms, or restrictions on product presentations. Their economic impact depends on whether the agreement grants market entry before patent expiry and whether it permits multiple generic entrants.

What generic launch scenarios exist for Optiray?

Scenario	Timing effect	Market effect
No blocking patent	Approval can proceed after regulatory requirements are met	Rapid price pressure is possible
One approved generic	Moderate initial erosion	Brand may retain contracts and supply advantage
Multiple approved generics	Strong price competition	Hospital tenders become more aggressive
Patent litigation with stay	Delayed approval	Brand retains near-term share
Generic approval but limited supply	Limited practical erosion	Brand supply reliability becomes valuable
Generic with different packaging	Partial substitution	Injector compatibility may preserve brand demand
Shortage-driven market	Temporary pricing resilience	Manufacturing capacity becomes decisive

Revenue exposure is not reliably measurable from public brand-level filings if Optiray revenue is reported within a broader contrast-media portfolio. The highest-exposure customers are hospitals, outpatient imaging networks, emergency departments, and high-volume CT centers. A generic entrant would likely target the largest iodine concentrations and the most standardized procedure volumes first.

How does Optiray compare with other iodinated contrast agents?

Optiray's excipient architecture is broadly consistent with the commercial design of nonionic iodinated contrast media: an aqueous vehicle, pH control, and protection against trace-metal-catalyzed degradation. Differentiation is therefore more likely to come from active ingredient properties, iodine concentration, osmolality, viscosity, injector performance, packaging, and supply reliability.

Criterion	Optiray	Key commercial implication
Active ingredient	Ioversol	Direct generic substitution is possible
Formulation complexity	Low	Lower formulation barrier
Excipient differentiation	Limited	Narrow technical claims are needed
Packaging differentiation	Meaningful	Supports lifecycle management
Biosimilar risk	None	Small-molecule competition applies
Manufacturing barrier	Moderate to high	Sterility and scale limit effective entry
Clinical switching barrier	Moderate	Protocols and injector workflows matter
Patent-based moat	Likely limited for mature product	Trade secrets and contracts gain importance

Key Takeaways

• Optiray contains ioversol in an aqueous formulation using tromethamine, calcium disodium edetate, hydrochloric acid for pH adjustment, and water for injection.
• The excipient system is functional and commercially mature, limiting the value of broad composition patents.
• The strongest lifecycle opportunities are high-concentration stability, injector-compatible packaging, container systems, reduced waste, and manufacturing reliability.
• Biosimilar competition does not apply because ioversol is a small molecule.
• Generic competition depends on FDA approval, patent listings, Paragraph IV activity, sterile manufacturing capacity, and distribution reliability.
• Trade secrets covering compounding, trace-metal control, filtration, filling, and container compatibility may have greater practical value than broad formulation patents.
• Optiray revenue exposure is likely embedded in a broader contrast-media portfolio rather than separately reported.
• Any current patent, litigation, settlement, or Orange Book conclusion must be tied to a specific patent number, NDA, ANDA, docket, and effective date.

FAQs

Is tromethamine in Optiray a patentable excipient?

Tromethamine alone is unlikely to support a commercially strong patent position. A defensible claim would need to cover a specific concentration range, formulation condition, or technical result such as improved high-iodine stability or reduced particulate formation.

Does Optiray contain sodium?

The commercial significance of sodium content depends on the exact product presentation and current labeling. The FDA-approved label should control any sodium-content assessment for procurement, clinical, or regulatory analysis.

Can a generic manufacturer use the same Optiray excipients?

A generic manufacturer may use the same inactive ingredients if the product meets applicable regulatory requirements and does not infringe enforceable patent claims. It does not necessarily need to use the same supplier, container, process, or commercial package.

Are Optiray and Omnipaque interchangeable?

They are competing iodinated contrast agents, not automatically interchangeable products. Substitution depends on iodine concentration, procedure, institutional protocol, injector settings, labeling, procurement policy, and clinician judgment.

Is Optiray protected by biologic exclusivity?

No. Optiray contains ioversol, a small-molecule active ingredient. Biologic reference-product exclusivity and biosimilar approval rules are not the applicable framework.

References

1. U.S. Food and Drug Administration. (2024a). Optiray (ioversol injection) prescribing information.
2. U.S. Food and Drug Administration. (2024b). Approved drug products with therapeutic equivalence evaluations.
3. U.S. Food and Drug Administration. (2024c). Orange Book: Approved drug products with therapeutic equivalence evaluations.
4. U.S. Congress. (1984). Drug Price Competition and Patent Term Restoration Act of 1984, Pub. L. No. 98-417.
5. Guerbet. (2024). Optiray product information and radiology contrast-media portfolio materials.