List of Excipients in Branded Drug ETHACRYNATE SODIUM

Generic Drugs Containing ETHACRYNATE SODIUM

Company	Ingredient	NDC	Excipient
Par Health USA LLC	ethacrynate sodium	42023-157	MANNITOL
Zydus Pharmaceuticals USA Inc	ethacrynate sodium	68382-246	MANNITOL
Leading Pharma LLC	ethacrynate sodium	69315-701	MANNITOL
Zydus Lifesciences Limited	ethacrynate sodium	70771-1106	MANNITOL

What are the Most Frequently-Used Excipients in ETHACRYNATE SODIUM?

# Of NDCs	Excipient
4	MANNITOL

Ethacrynate Sodium Excipient Strategy and Commercial Opportunities

Last updated: September 24, 2026

Ethacrynate sodium is the injectable sodium salt of ethacrynic acid, a loop diuretic used when rapid diuresis is required or when a sulfonamide-containing loop diuretic may be unsuitable. Its commercial opportunity is limited by low volume, safety concerns, legacy-product status and competition from furosemide, bumetanide and torsemide. The strongest formulation opportunities are injectable stability, ready-to-use hospital presentations, low-volume reconstitution, oral liquid dosing and excipient systems that reduce administration errors.

What is ethacrynate sodium and how is it used?

Ethacrynate sodium is administered intravenously after reconstitution. The active moiety, ethacrynic acid, inhibits the Na-K-2Cl cotransporter in the thick ascending limb of the loop of Henle. It is generally reserved for patients requiring potent diuresis, including patients with congestive heart failure, hepatic disease, renal disease or sulfonamide hypersensitivity concerns.

The principal commercial product is Edecrin, which has been marketed in oral ethacrynic acid tablets and injectable ethacrynate sodium presentations. FDA labeling identifies the injection as a sterile lyophilized or dry formulation requiring reconstitution before administration. The product is hospital-oriented rather than a high-volume retail medicine.[1]

Key product attributes

Attribute	Ethacrynate sodium
Active moiety	Ethacrynic acid
Drug class	Loop diuretic
Primary route	Intravenous for ethacrynate sodium
Oral counterpart	Ethacrynic acid tablets
Main clinical niche	Potent diuresis, including patients with sulfonamide allergy concerns
Primary commercial channel	Hospitals, emergency care and specialty pharmacy
Main competitors	Furosemide, bumetanide and torsemide
Principal formulation risk	Stability, reconstitution and ototoxicity-related dose control
Patent profile	Legacy active ingredient with no credible basis for assuming active composition-of-matter protection

What excipients are used in ethacrynate sodium injection?

The core excipient requirement is a stable, water-soluble sodium salt that can be reconstituted rapidly for intravenous administration. Public labeling for legacy ethacrynate sodium injection identifies mannitol as a principal inactive ingredient in the vial presentation, with sterile water used for reconstitution.[1,2]

Mannitol is commercially logical because it can:

• Improve cake structure in a lyophilized product.
• Provide bulking capacity at low drug load.
• Support an acceptable reconstitution profile.
• Avoid chloride, sulfate and other counterions that may complicate parenteral formulation.
• Fit existing hospital compounding practices.

The formulation must control pH because ethacrynic acid has limited intrinsic aqueous solubility, while the sodium salt is more soluble under alkaline conditions. Excessively alkaline conditions can increase chemical degradation, cause infusion-site concerns or reduce compatibility with other intravenous products.

Likely excipient functions

Excipient category	Potential role	Commercial relevance
Mannitol	Bulking agent and lyophilization aid	Established hospital-injection profile
Sodium hydroxide or other alkalinizing agent	pH adjustment and salt formation	May improve solubility
Hydrochloric acid or equivalent acid	Final pH adjustment	Requires tight control to avoid precipitation
Water for injection	Reconstitution vehicle	Standard hospital administration
Nitrogen headspace	Oxygen reduction	May reduce oxidative degradation
Surfactant	Wetting or reconstitution support	Must be justified for parenteral safety
Buffer system	pH control	May affect compatibility and stability
Antioxidant or chelator	Oxidative degradation control	Requires impurity and safety assessment

A preservative-free single-dose vial is the most defensible commercial design. A multidose presentation would create preservative, sterility, compatibility and labeling burdens without an obvious commercial advantage in a low-volume emergency-care product.

What excipient strategy is most suitable for ethacrynate sodium?

The preferred strategy is a conservative parenteral platform based on a lyophilized sodium salt, mannitol, controlled alkalinity and a short reconstitution time.

Recommended reference formulation concept

Formulation element	Recommended approach
Drug substance	Ethacrynate sodium with controlled water and residual-solvent specifications
Dosage form	Sterile lyophilized powder
Bulking agent	Mannitol or a mannitol-dominant system
pH	Mildly alkaline after reconstitution, within validated product limits
Container	Type I glass vial with elastomeric stopper
Presentation	Single-dose vial
Reconstitution	Sterile water for injection
Administration	Direct intravenous injection or validated dilution into compatible fluid
Oxygen control	Nitrogen flushing or low-oxygen fill environment if degradation supports the approach
Preservatives	Preferably none

A reformulator should avoid unnecessary excipients. Ethacrynate sodium has a narrow commercial niche, and each additional excipient creates a new burden for extractables and leachables, parenteral safety, particulate control, compatibility and regulatory justification.

What formulation patents could protect an ethacrynate sodium product?

New composition-of-matter protection for ethacrynate sodium is unlikely to be available because the active ingredient is an established drug. Commercial protection would need to come from formulation, device, process or use claims.

Potential claim areas include:

1. Stable lyophilized composition
   Claims could cover ethacrynate sodium, mannitol and a defined residual-moisture range that improves stability.

2. Reconstitution performance
   A product could be differentiated by reconstitution in less than a defined period, reduced foaming or reduced undissolved particulate matter.

3. Ready-to-use solution
   A stable premixed intravenous solution in a specific container, concentration and pH range could support a formulation patent if the stability data show an unexpected result.

4. Container-closure system
   Claims could cover a vial, syringe or cartridge that limits adsorption, oxidation or moisture ingress.

5. Administration device
   A prefilled syringe, dose-confirming system or closed-transfer device could create device claims, although the commercial value would depend on hospital workflow.

6. Stability-indicating manufacturing process
   Claims could address oxygen control, lyophilization cycle parameters, moisture limits or impurity reduction.

7. Patient-selection or method-of-use claims
   Use claims for patients with sulfonamide hypersensitivity or specific renal and hepatic conditions may be possible, but their practical exclusivity is often weaker than formulation claims.

The main patent risk is that broad claims may be vulnerable to prior art involving legacy ethacrynic acid formulations, generic lyophilized injections and standard parenteral excipient systems. A robust filing would need comparative stability data, not only routine formulation screening.

What is the FDA regulatory status of ethacrynate sodium?

Ethacrynate sodium has an established FDA regulatory history through Edecrin and related ethacrynic acid products. The product is not a new molecular entity. A new sponsor would likely evaluate one of three pathways:

Regulatory pathway	Potential use
ANDA under section 505(j)	Generic equivalent to a listed reference product if a suitable reference and dosage-form pathway are available
505(b)(2) NDA	Reformulated, ready-to-use, new-concentration or otherwise differentiated product relying partly on FDA findings for the established drug
Full 505(b)(1) NDA	Unlikely commercial choice unless the sponsor cannot rely on existing findings

The regulatory pathway depends on the current reference-listed drug, dosage form, route, labeling, product availability and FDA determinations. A sterile injectable product must address sterility assurance, particulate matter, endotoxins, container-closure integrity, extractables and leachables, assay, impurities, pH, osmolality and reconstitution performance.

FDA development priorities

A development program should generate:

• Accelerated and long-term stability data.
• Photostability data.
• Reconstitution-time and solution-clarity data.
• Compatibility data with common intravenous fluids.
• In-use stability after reconstitution.
• Particulate and subvisible-particle data.
• Container-closure integrity.
• Forced-degradation profiles.
• Leachables and extractables data.
• Comparative impurity profiling against the reference product.

When does ethacrynate sodium lose exclusivity?

Ethacrynate sodium’s original active-ingredient exclusivity is historical and has expired. The main commercial barriers are therefore regulatory and technical rather than basic compound patent rights.

Exclusivity profile

Protection type	Current commercial assessment
Composition-of-matter patent	Expected to be expired
Original product patent	Expected to be expired
New chemical entity exclusivity	Expired
Pediatric exclusivity	No current basis for assuming active protection
Orphan exclusivity	Not the principal historical protection
Formulation exclusivity	Product-specific; requires current Orange Book and FDA review
Method-of-use exclusivity	Must be verified against current FDA listings
Generic exclusivity	Depends on approved ANDAs and Paragraph IV events
Biosimilar exclusivity	Not applicable

A precise current Orange Book conclusion requires review of the live FDA Orange Book entry for the relevant Edecrin and ethacrynate sodium products. Historical patent expiration does not by itself establish whether a later formulation patent remains listed or enforceable.

What is the Orange Book status of ethacrynate sodium?

Ethacrynate sodium is a small-molecule drug and is evaluated under the Orange Book framework rather than the Purple Book biosimilar framework. Orange Book analysis should distinguish between:

• Ethacrynic acid tablets.
• Ethacrynate sodium injection.
• The specific reference-listed drug.
• Any listed patents or exclusivity codes.
• Product availability and discontinuation status.
• Whether the relevant product is eligible for ANDA referencing.

The practical diligence question is whether a sponsor can file an ANDA against a currently referenceable product or must pursue a 505(b)(2) route because the desired presentation differs from the listed product.

What Paragraph IV challenges and litigation affect ethacrynate sodium?

Ethacrynate sodium has a low-profile litigation history compared with major branded medicines. No significant current Paragraph IV campaign should be assumed without a live review of FDA ANDA records, Orange Book patent listings and federal court dockets.

For a new entrant, the likely litigation exposure is limited to:

• A Paragraph IV certification against any listed formulation patent.
• Patent infringement claims involving a newly approved formulation.
• Trade-secret or contract disputes involving manufacturing processes.
• Product liability claims linked to dosing errors, ototoxicity or infusion complications.
• Regulatory exclusivity disputes tied to reference-product status.

The absence of prominent litigation does not establish freedom to operate. Legacy patents can expire while newer patents covering a specific ready-to-use concentration, container or stability system remain relevant.

How strong is the patent estate for ethacrynate sodium?

The underlying patent estate is weak by branded-pharmaceutical standards because the active ingredient is old and generic substitution is technically feasible. A reformulated product could create a moderate patent position only if it delivers a measurable technical improvement.

Patent-strength assessment

Asset type	Expected strength
Active ingredient	Low
Basic sodium salt formulation	Low
Mannitol-containing lyophilized vial	Low to moderate
Narrow stability range supported by comparative data	Moderate
Ready-to-use formulation with unexpected stability	Moderate to strong if enabled
Prefilled syringe or delivery device	Moderate, depending on integration
Broad method-of-use claims	Low to moderate
Manufacturing process claims	Moderate if difficult to design around

The best protection would combine a formulation patent with trade secrets covering drug-substance controls, lyophilization parameters, moisture limits and container selection.

What commercial opportunities exist for ethacrynate sodium?

The commercial opportunity is a focused hospital product, not a mass-market generic. Potential opportunities include:

1. Ready-to-use injectable

A premixed or prefilled presentation could eliminate vial reconstitution and reduce medication-preparation time. The commercial case depends on demonstrating acceptable stability and pricing the product against pharmacy labor, waste and medication-error costs.

2. Improved lyophilized vial

A smaller vial, faster reconstitution time or clearer labeling could compete with legacy presentations. This is the lowest-risk development option if the reference formulation is available for comparison.

3. Hospital shortage product

Ethacrynate sodium can occupy a shortage-resilience niche because it is clinically differentiated from sulfonamide-containing loop diuretics. A manufacturer with sterile-injectable capacity could target hospital contracts and group purchasing organizations.

4. Pediatric or dose-flexible presentation

A lower-strength vial or a validated oral liquid could improve dose flexibility. Pediatric development would require careful attention to taste masking, preservative selection, dosing accuracy and excipient exposure.

5. International licensing

A regional license can be attractive where hospitals lack reliable access to ethacrynic acid products. The opportunity is strongest in markets with high demand for loop diuretics and limited access to non-sulfonamide alternatives.

6. Contract manufacturing

A manufacturer with lyophilization capacity, Type I glass filling and low-volume injectable experience could offer ethacrynate sodium as a portfolio product alongside other hospital injectables.

How does ethacrynate sodium compare with competing loop diuretics?

Product	Sulfonamide-related concern	Typical commercial position	Formulation opportunity
Ethacrynate sodium	No sulfonamide group	Specialty or rescue use	Ready-to-use injectable and shortage supply
Furosemide	Contains sulfonamide structure	Dominant high-volume loop diuretic	Cost and supply efficiency
Bumetanide	Contains sulfonamide structure	Potent, lower-dose alternative	Concentrated injectable and oral products
Torsemide	Contains sulfonamide structure	Chronic oral heart-failure use	Long-acting oral products

Ethacrynate sodium cannot compete primarily on price. Its value proposition is clinical differentiation, injectable availability, non-sulfonamide positioning and reliable hospital supply.

What manufacturing and IP barriers exist?

The most important barriers are sterile manufacturing and product quality rather than active-ingredient synthesis. Key manufacturing risks include:

• Low-dose uniformity.
• Control of sodium-salt formation.
• Moisture sensitivity.
• Oxidative degradation.
• Reconstitution variability.
• Particulate generation.
• Stopper interaction.
• Vial adsorption.
• Batch-to-batch impurity control.
• Limited commercial scale.

The active ingredient may be sourced from a small number of qualified manufacturers. A dual-source strategy is important because a single-source drug substance can create supply risk even when the product has no meaningful patent barrier.

What licensing deals are relevant?

No major, widely disclosed current licensing transaction should be treated as a benchmark for ethacrynate sodium. Commercial deals would more likely involve:

• Regional marketing rights.
• Transfer of an approved injectable product.
• Contract manufacturing and supply.
• Acquisition of a legacy hospital product.
• Co-development of a ready-to-use formulation.
• Licensing of a sterile-fill or lyophilization platform.

The most valuable licensable asset would be an approved product with demonstrated hospital demand, not a broad ethacrynate sodium patent. A deal should prioritize regulatory status, supply continuity, manufacturing redundancy and any listed formulation patents.

Key Takeaways

• Ethacrynate sodium is a legacy loop diuretic with a narrow but defensible hospital niche.
• The strongest excipient platform is a preservative-free, single-dose lyophilized vial using mannitol and controlled pH.
• Ready-to-use and prefilled presentations offer the clearest commercial differentiation.
• Active-ingredient patent protection is expected to be expired; formulation and process claims are the principal remaining IP tools.
• An ANDA may be appropriate for a direct generic, while a differentiated ready-to-use product may require a 505(b)(2) strategy.
• Biosimilar risk does not apply because ethacrynate sodium is a small-molecule drug.
• The key barriers are sterile manufacturing, stability, reconstitution performance and hospital economics.
• Commercial success depends on supply reliability and workflow advantages rather than premium pricing based solely on the active ingredient.

FAQs

Is ethacrynate sodium the same as ethacrynic acid?

No. Ethacrynate sodium is the sodium salt used for injectable administration, while ethacrynic acid is the active drug commonly associated with oral tablets. Both deliver the same active moiety after administration.

Can mannitol be replaced in an ethacrynate sodium injection?

Potentially. Trehalose, sucrose or other lyophilization excipients could be evaluated, but replacement would require new stability, reconstitution, sterility and compatibility data. Mannitol remains the most commercially conservative starting point.

Is ethacrynate sodium eligible for biosimilar development?

No. Biosimilar pathways apply to biological products. Ethacrynate sodium is a chemically synthesized small-molecule drug and is addressed through ANDA or NDA pathways.

What is the most valuable improvement for an ethacrynate sodium product?

A stable ready-to-use or prefilled intravenous presentation is likely the most valuable improvement because it can reduce reconstitution steps, pharmacy workload and medication-preparation risk.

Does ethacrynate sodium have strong generic-entry potential?

Yes, if a current reference product and viable sterile manufacturing pathway are available. The market is small, but the absence of meaningful active-ingredient exclusivity lowers the primary IP barrier.

References

1. U.S. Food and Drug Administration. (n.d.). Edecrin (ethacrynic acid) and Edecrin sodium prescribing information. FDA/DailyMed.
2. National Library of Medicine. (n.d.). Ethacrynate sodium injection product labeling. DailyMed.
3. U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations. FDA.
4. U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs database. FDA.
5. U.S. Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations. FDA.