List of Excipients in Branded Drug METHOHEXITAL SODIUM

Generic Drugs Containing METHOHEXITAL SODIUM

Company	Ingredient	NDC	Excipient
Heritage Pharmaceuticals Inc d/b/a Avet Pharmaceuticals Inc	methohexital sodium	23155-893	SODIUM CARBONATE
Heritage Pharmaceuticals Inc d/b/a Avet Pharmaceuticals Inc	methohexital sodium	23155-893	SODIUM HYDROXIDE
ONESOURCE SPECIALTY PHARMA LIMITED	methohexital sodium	83270-003	SODIUM CARBONATE
ONESOURCE SPECIALTY PHARMA LIMITED	methohexital sodium	83270-003	SODIUM HYDROXIDE

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

# Of NDCs	Excipient
2	SODIUM CARBONATE
2	SODIUM HYDROXIDE

Methohexital Sodium Excipient Strategy and Commercial Opportunities

Last updated: September 24, 2026

Methohexital sodium is an established ultra-short-acting barbiturate anesthetic supplied primarily as a sterile powder for reconstitution. The strongest commercial opportunities are differentiated injectable presentations: ready-to-use solutions, controlled-reconstitution vials, low-waste packaging, and products optimized for anesthesia workstations and procedural sedation. The core formulation challenge is maintaining solubility and chemical stability in an alkaline aqueous system while avoiding precipitation, incompatibility, microbial risk, and administration errors.

What is the formulation profile of methohexital sodium?

Methohexital is marketed as the water-soluble sodium salt of methohexital, an ester-type barbiturate used for induction of general anesthesia and short procedures. FDA labeling identifies methohexital sodium for intravenous use and, in some products, intramuscular or rectal administration when clinically appropriate.[1]

The conventional product is a sterile lyophilized or dry powder that requires reconstitution before administration. The label generally directs reconstitution with sterile water for injection. Depending on product labeling, sodium chloride injection or dextrose injection may be permitted for dilution after reconstitution.[1,2]

Attribute	Commercial relevance
Active ingredient	Methohexital sodium
Therapeutic class	Ultra-short-acting barbiturate anesthetic
Primary route	Intravenous
Dosage form	Sterile powder for injection; some markets may have solution products
Typical use	Induction of anesthesia and brief procedural anesthesia
Formulation sensitivity	Alkaline pH, precipitation risk after dilution, compatibility constraints
Main users	Hospitals, ambulatory surgery centers, anesthesia departments, emergency and procedural units
Primary alternatives	Propofol, etomidate, ketamine, thiopental where available
Main commercial issue	Administration convenience and supply reliability rather than basic molecule differentiation

Methohexital sodium is highly water-soluble in its alkaline salt form. The formulation cannot be treated as a conventional neutral-pH injectable. The pH, buffer capacity, ionic environment, container closure system, and dilution instructions directly affect product performance.

Which excipients are suitable for methohexital sodium injection?

The most defensible excipient strategy is a minimal-excipient formulation based on the sodium salt, water for injection, and tightly controlled pH adjustment. Excess excipient loading can create compatibility, toxicity, osmolality, and regulatory burdens without delivering a meaningful clinical benefit.

Water for injection

Water for injection is the primary vehicle for a reconstituted presentation. It supports rapid dissolution and is the conventional diluent specified in methohexital labeling.[1]

Commercial advantages include:

• Simple composition and familiar hospital handling.
• Low regulatory complexity.
• Compatibility with standard sterile injectable manufacturing.
• Lower risk of excipient-related hypersensitivity claims.
• Easier global registration where excipient restrictions differ.

A ready-to-use aqueous product would require a stability package that addresses potency, degradation products, pH drift, container interaction, and particulate formation throughout the proposed shelf life.

Sodium hydroxide and pH control

Methohexital sodium solutions are alkaline. Sodium hydroxide may be used for pH adjustment or alkalinity control, depending on the product design and manufacturing process. The target pH should be established through forced-degradation, solubility, compatibility, and clinical tolerability studies rather than copied from a different barbiturate formulation.

The commercial problem is a narrow operating window:

• Insufficient alkalinity can increase precipitation risk.
• Excess alkalinity can increase tissue irritation and administration risk.
• pH drift can affect potency, degradation, and compatibility with co-administered drugs.
• A highly alkaline solution can limit Y-site and syringe compatibility.

A strong formulation program would define a pH range with demonstrated performance after manufacture, storage, reconstitution, dilution, and administration.

Sodium chloride and dextrose

Sodium chloride injection and dextrose injection can be relevant as dilution media where permitted by the applicable label. They are not necessarily optimal as primary formulation vehicles. Their principal value is operational: they align with hospital inventory and existing infusion practices.

The formulation developer should evaluate:

• Precipitation after dilution.
• Stability at clinically relevant concentrations.
• Compatibility with infusion bags, syringes, and tubing.
• Container adsorption or extractables.
• Maximum hold time after dilution.
• Temperature effects in operating-room workflows.

A product label that provides clear dilution limits and hold times can reduce nursing and pharmacy uncertainty. The label must not imply compatibility with all commonly used anesthetic or emergency drugs.

Preservatives

A preservative-free presentation is preferable for single-dose intravenous use. Preservatives can create additional toxicity and compatibility concerns and may restrict use in neonates, pediatric patients, or neuraxial settings. A multidose presentation could reduce packaging cost but would require a strong antimicrobial-preservation rationale and careful assessment of repeated access, contamination risk, and clinical setting.

For methohexital, the commercial value of preservative-free packaging is likely higher than the value of a multidose vial because the principal users are controlled procedural environments where single-dose administration is standard.

Chelators, surfactants, and antioxidants

EDTA, polysorbates, sulfites, and other stabilizing excipients should not be added without a demonstrated need. Their potential roles include metal-ion control, interfacial stabilization, or oxidation protection, but each can create new regulatory and clinical liabilities.

A low-excipient formulation is commercially attractive because it:

• Simplifies the inactive-ingredient profile.
• Reduces label-comparison issues for an ANDA.
• Limits new safety questions.
• Eases global excipient review.
• Supports preservative-free positioning.

What formulations are protected by methohexital sodium patents?

Methohexital sodium is an old active pharmaceutical ingredient with extensive historical use. The principal competitive barrier is unlikely to be basic composition-of-matter protection. Commercial protection would more likely arise from formulation, container, device, manufacturing, or method-of-use claims.

Potentially protectable areas include:

1. A stable ready-to-use methohexital sodium solution.
2. A defined pH and concentration range that prevents precipitation.
3. A dual-chamber vial separating methohexital from the aqueous vehicle until use.
4. A prefilled syringe with validated chemical and physical stability.
5. A low-volume formulation designed for rapid procedural dosing.
6. A formulation with extended post-reconstitution hold time.
7. A manufacturing process that reduces degradation or particulate formation.
8. A packaging system that improves light, oxygen, or moisture protection.
9. A device-linked presentation that controls reconstitution or dose delivery.

These claims require a technical effect. A patent based only on selecting a common diluent or repackaging a known product would face substantial obviousness and enablement pressure.

When does methohexital sodium lose exclusivity?

Methohexital sodium has long passed the period of ordinary small-molecule product exclusivity. Current market access is therefore driven by abbreviated approval, manufacturing capacity, supply reliability, product quality, and institutional contracting.

Exclusivity category	Methohexital sodium position
New chemical entity exclusivity	Expired
Basic composition patent	Historical protection has expired or is commercially immaterial
Conventional injectable formulation	Generally open to generic competition, subject to applicable approvals
Pediatric exclusivity	No generally relevant current exclusivity identified
Orphan exclusivity	Not a primary market protection for the conventional anesthetic use
Biosimilar exclusivity	Not applicable; methohexital is a small molecule
Formulation patents	Possible for new differentiated presentations
Method-of-use patents	Possible but narrow and potentially vulnerable if based on established uses

An applicant should verify current patent and exclusivity records through FDA Drugs@FDA, the Approved Drug Products with Therapeutic Equivalence Evaluations database, and applicable patent litigation records before filing or investing.[3,4]

What is the Orange Book status of methohexital sodium?

The Orange Book is relevant for approved drug products, therapeutic-equivalence ratings, patents submitted for listing, and exclusivity. Methohexital sodium products may appear under product-specific entries rather than under a single broad “methohexital” category. Listing status can differ by strength, dosage form, manufacturer, and approval history.

For a generic strategy, the practical Orange Book questions are:

• Is the reference listed drug currently approved?
• Which strength and presentation is the reference product?
• Does the reference have a therapeutic-equivalence rating?
• Are any patents or exclusivities listed for the target product?
• Is the proposed product eligible for an ANDA or does it require a different pathway?
• Does the applicant need a Paragraph IV certification?

A Paragraph IV certification is relevant only when an ANDA applicant challenges a listed patent as invalid, unenforceable, or not infringed. For an old injectable such as methohexital sodium, the main risk is likely to arise from later-added formulation or device patents rather than from the original active ingredient.

Which companies are challenging or competing with methohexital sodium?

Competition is broader than direct methohexital generic competition. Hospitals select among anesthetic products based on onset, recovery, hemodynamic profile, seizure considerations, drug shortages, workflow, and acquisition cost.

Competitor	Commercial position
Propofol	Dominant alternative for many induction and procedural uses; ready-to-use injectable formats are operationally convenient
Etomidate	Used where cardiovascular stability is prioritized
Ketamine	Provides dissociative anesthesia and analgesia; different clinical profile
Thiopental	Historical barbiturate comparator; availability varies by market
Methohexital sodium	Useful for rapid induction and selected procedural, neurologic, and electroconvulsive therapy settings

Methohexital can compete more effectively where clinicians value rapid onset and short duration but want an alternative to propofol or ketamine. Commercial uptake depends on whether the product is available in a format that fits current anesthesia workflows.

What excipient strategies create the best commercial opportunities?

Ready-to-use liquid formulation

A ready-to-use solution could eliminate reconstitution steps, lower preparation errors, and improve time-to-administration. Its development burden is higher because the product must remain stable as a liquid through the proposed shelf life.

Key targets include:

• Stable concentration suitable for common induction doses.
• Low injection volume.
• Preservative-free single-dose packaging.
• Clear visual inspection.
• Compatibility with polypropylene syringes and standard IV components.
• Robust stability under controlled room-temperature conditions.

Dual-chamber vial

A dual-chamber system separates the dry drug from the diluent until activation. It can preserve the stability advantages of a powder while reducing manual reconstitution steps.

Its disadvantages are higher device cost, more complex human-factors validation, and potentially more difficult hospital stocking. The business case is strongest where reconstitution errors or preparation delays have documented operational consequences.

Prefilled syringe

A prefilled syringe could support emergency anesthesia carts, procedural areas, and ambulatory surgery centers. The main barriers are chemical stability, syringe-material compatibility, dose flexibility, and cost per administration.

A commercial product may need multiple strengths or fill volumes. A single fixed dose would limit use across adult patient weights and clinical indications.

Lyophilized vial with improved reconstitution

This is the lowest-risk development path. Improvements may include:

• Faster dissolution.
• Reduced foaming.
• Clearer reconstitution instructions.
• Better vial fill accuracy.
• Smaller vial size.
• Reduced residual drug waste.
• Packaging optimized for automated pharmacy systems.

This strategy is less likely to produce broad patent protection but can generate a practical hospital product with lower development risk.

How strong is the patent estate for methohexital sodium?

The underlying patent estate is likely weak for the legacy molecule and conventional powder-for-injection product. A new formulation estate could be stronger if it demonstrates an unexpected technical effect, such as materially improved stability, reduced precipitation, lower particulate burden, or a clinically meaningful reduction in preparation time.

Patent target	Relative strength
Methohexital sodium compound	Low for new exclusivity
Conventional sterile powder	Low to moderate
Defined liquid pH and concentration	Moderate if supported by unexpected stability
Ready-to-use solution	Moderate to strong if stability is difficult to achieve
Dual-chamber delivery system	Moderate, often dependent on device claims
Prefilled syringe	Moderate, with design-around risk
Reconstitution method	Low to moderate unless it solves a documented technical problem
Manufacturing impurity-control process	Moderate if impurity reduction is reproducible and non-obvious
Broad method-of-use claims	Low to moderate because many uses are established

Patent drafting should use layered claims: composition, concentration, pH, impurity profile, container, storage condition, reconstitution method, and use. A single narrow formulation claim would be easier to design around.

What manufacturing and IP barriers affect commercial entry?

The main technical barriers are sterile manufacturing, control of alkaline solutions, particulate control, container compatibility, and reliable supply of API. Methohexital sodium is not a high-volume chronic medicine, so manufacturing economics can be unfavorable unless the product commands a premium for convenience or supply assurance.

Important development controls include:

• API identity, assay, related substances, and residual solvents.
• Control of moisture in the sterile powder.
• Lyophilization-cycle reproducibility.
• Reconstitution time.
• Visible and subvisible particulate limits.
• Container-closure integrity.
• Extractables and leachables.
• Stability after dilution.
• In-use stability during operating-room handling.
• Sterility assurance and endotoxin control.

A vertically integrated manufacturer with sterile injectable capacity has an advantage over a marketing company dependent on a single contract manufacturer. Hospitals may value continuity of supply because anesthetic shortages can disrupt operating-room schedules.

What generic launch scenarios exist for methohexital sodium?

Conventional generic powder

This has the lowest development cost and the greatest price pressure. It competes primarily through availability, contract pricing, and reliable quality.

Premium convenience product

A ready-to-use syringe, solution, or dual-chamber vial can support a higher price if it reduces preparation time and waste. The product must demonstrate operational value to pharmacy and anesthesia departments.

Shortage-response product

A manufacturer can target hospitals and group purchasing organizations seeking a second source. This opportunity depends on FDA approval, validated sterile capacity, and inventory commitments rather than patent exclusivity.

Specialty procedural product

A product packaged for electroconvulsive therapy, pediatric anesthesia, or ambulatory surgery may achieve focused adoption. Method-of-use claims would need to avoid covering established clinical practice without a defensible technical distinction.

How does methohexital sodium compare with propofol?

Propofol generally has stronger workflow advantages because it is widely available as a ready-to-use emulsion. Methohexital can differentiate through its barbiturate pharmacology, rapid onset, and suitability for selected clinical settings. Propofol’s emulsion also has its own handling, microbial, and compatibility considerations.

Factor	Methohexital sodium	Propofol
Conventional form	Powder requiring reconstitution	Ready-to-use emulsion
Formulation burden	Alkaline solution and precipitation control	Emulsion stability and microbial control
Workflow	More preparation steps	Direct administration
Differentiation opportunity	Convenience, stability, packaging	Device and emulsion improvements
Biosimilar risk	None	None; small molecule
Price pressure	High for standard generic	High but offset by broad use
Commercial whitespace	Ready-to-use, low-waste, shortage-resilient products	Specialized emulsions and delivery systems

What is the FDA regulatory pathway for a new methohexital product?

A conventional generic injectable would generally be evaluated through an ANDA if a suitable reference listed drug exists and the product can demonstrate pharmaceutical equivalence and bioequivalence under the applicable framework.[3] A materially different formulation, delivery system, or clinical use may require a different regulatory strategy.

The development package should address:

• Same active ingredient and dosage form.
• Equivalent strength and route.
• Inactive-ingredient justification.
• Sterility and endotoxin controls.
• Comparative dissolution or reconstitution performance where applicable.
• Stability and in-use data.
• Container-closure compatibility.
• Labeling conformity.
• Device performance for combination products.

A new ready-to-use formulation may have greater regulatory value but also greater clinical and chemistry, manufacturing, and controls requirements.

Key Takeaways

• Methohexital sodium is an old injectable anesthetic with limited value in basic molecule exclusivity.
• The strongest commercial opportunities are formulation and packaging improvements.
• Water for injection and controlled alkalinity are the core excipient elements.
• Preservative-free single-dose products are better aligned with intravenous anesthesia use than multidose formats.
• A ready-to-use solution, prefilled syringe, or dual-chamber vial could reduce reconstitution burden and create differentiated commercial value.
• Patent strength depends on demonstrated stability, precipitation control, impurity reduction, or device performance.
• Generic competition is likely to be price-sensitive, making supply reliability and workflow economics central to market access.
• The principal competitive threat is propofol, not only other methohexital products.
• Methohexital has no biosimilar pathway because it is a small-molecule drug.
• FDA Orange Book, Drugs@FDA, patent listings, and litigation records must be reviewed for the specific reference product and target presentation before filing.

FAQs

Can methohexital sodium be formulated without preservatives?

Yes. A preservative-free single-dose vial, prefilled syringe, or ready-to-use unit is technically and commercially preferable for many intravenous applications, provided sterility and container-closure integrity are demonstrated.

Is methohexital sodium compatible with normal saline?

Compatibility depends on concentration, pH, dilution conditions, storage duration, and the specific product label. The formulation must be tested for precipitation, potency, particulate matter, and container interaction after dilution.

Can a ready-to-use methohexital sodium injection receive patent protection?

Yes, if the formulation provides a non-obvious technical result such as improved liquid stability, reduced precipitation, lower impurity formation, or a validated container-delivery advantage. A simple substitution of a known diluent would offer weaker protection.

Is methohexital sodium a biologic or biosimilar product?

No. Methohexital sodium is a synthetic small-molecule drug. Marketed competitors are generics or differentiated formulations, not biosimilars.

What is the most attractive commercial presentation for methohexital sodium?

A preservative-free, ready-to-use, low-volume injectable with validated room-temperature stability and clear compatibility instructions offers the strongest combination of workflow value and product differentiation.

References

1. DailyMed. (n.d.). Methohexital sodium for injection prescribing information. U.S. National Library of Medicine.

2. Fresenius Kabi USA, LLC. (n.d.). Brevital sodium (methohexital sodium for injection) prescribing information. U.S. Food and Drug Administration labeling archive.

3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA.

4. U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs database. FDA.